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Gene Information
Gene symbol: IL4
Gene name: interleukin 4
HGNC ID: 6014
Synonyms: BSF1, IL-4, BCGF1, BCGF-1, MGC79402
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1528876 | An anergic, islet-infiltrating T-cell clone that suppresses murine diabetes secretes a factor that blocks interleukin 2/interleukin 4-dependent proliferation. |
| 2 | 1528876 | As we previously reported, an accelerated form of diabetogenic autoimmunity in nonobese diabetic mice can be blocked by passive transfer of a CD3+, CD8+, beta-chain variable region 11-positive islet-infiltrating T-cell clone (IS-2.15). |
| 3 | 1528876 | Moreover, these T cells secrete an inhibitory factor(s) that irreversibly inhibits interleukin (IL) 2/IL-4-driven proliferation of IL-2/IL-4 indicator T-cell lines. |
| 4 | 1528876 | These data indicate that at least some anergic T cells can play an active role in peripheral tolerance by secreting suppressor factor(s) that regulate IL-2/IL-4-dependent proliferation. |
| 5 | 1528876 | An anergic, islet-infiltrating T-cell clone that suppresses murine diabetes secretes a factor that blocks interleukin 2/interleukin 4-dependent proliferation. |
| 6 | 1528876 | As we previously reported, an accelerated form of diabetogenic autoimmunity in nonobese diabetic mice can be blocked by passive transfer of a CD3+, CD8+, beta-chain variable region 11-positive islet-infiltrating T-cell clone (IS-2.15). |
| 7 | 1528876 | Moreover, these T cells secrete an inhibitory factor(s) that irreversibly inhibits interleukin (IL) 2/IL-4-driven proliferation of IL-2/IL-4 indicator T-cell lines. |
| 8 | 1528876 | These data indicate that at least some anergic T cells can play an active role in peripheral tolerance by secreting suppressor factor(s) that regulate IL-2/IL-4-dependent proliferation. |
| 9 | 1528876 | An anergic, islet-infiltrating T-cell clone that suppresses murine diabetes secretes a factor that blocks interleukin 2/interleukin 4-dependent proliferation. |
| 10 | 1528876 | As we previously reported, an accelerated form of diabetogenic autoimmunity in nonobese diabetic mice can be blocked by passive transfer of a CD3+, CD8+, beta-chain variable region 11-positive islet-infiltrating T-cell clone (IS-2.15). |
| 11 | 1528876 | Moreover, these T cells secrete an inhibitory factor(s) that irreversibly inhibits interleukin (IL) 2/IL-4-driven proliferation of IL-2/IL-4 indicator T-cell lines. |
| 12 | 1528876 | These data indicate that at least some anergic T cells can play an active role in peripheral tolerance by secreting suppressor factor(s) that regulate IL-2/IL-4-dependent proliferation. |
| 13 | 1751309 | These cells secrete predominantly interleukin-4, interleukin-5, and interleukin-10, and may contribute to a chronic response and autoimmune disease. |
| 14 | 1934594 | Cytokines are known to play an important role in autoimmunity and have been suggested to be involved in the pathogenesis of insulin-dependent diabetes (IDDM). |
| 15 | 1934594 | In the present study we have measured IL-1, IL-2, IL-4, IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) (using both immunoassays and bioassays) in sera from 50 patients affected by IDDM at the time of clinical diagnosis and 51 age and sex matched controls. |
| 16 | 1934594 | Detectable levels of IL-1, IL-2, IL-6 and IFN-gamma were found in the serum of a small percentage of subjects and were not significantly different between patients and controls. |
| 17 | 1934594 | IL-4 was detectable in a higher number of both patients and controls and circulating TNF-alpha (greater than 1 U/ml) was found in a percentage of patients (24%) significantly higher than controls (P less than 0.01). |
| 18 | 1934594 | Cytokines are known to play an important role in autoimmunity and have been suggested to be involved in the pathogenesis of insulin-dependent diabetes (IDDM). |
| 19 | 1934594 | In the present study we have measured IL-1, IL-2, IL-4, IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) (using both immunoassays and bioassays) in sera from 50 patients affected by IDDM at the time of clinical diagnosis and 51 age and sex matched controls. |
| 20 | 1934594 | Detectable levels of IL-1, IL-2, IL-6 and IFN-gamma were found in the serum of a small percentage of subjects and were not significantly different between patients and controls. |
| 21 | 1934594 | IL-4 was detectable in a higher number of both patients and controls and circulating TNF-alpha (greater than 1 U/ml) was found in a percentage of patients (24%) significantly higher than controls (P less than 0.01). |
| 22 | 7485382 | Suppression of insulitis in non-obese diabetic (NOD) mice by oral insulin administration is associated with selective expression of interleukin-4 and -10, transforming growth factor-beta, and prostaglandin-E. |
| 23 | 7485382 | Immunohistological studies using monoclonal antibodies showed that infiltrating MNC consisted mainly of CD4+ T cells ( > 75% of leukocytes) plus smaller numbers of macrophages and CD8+ T cells. |
| 24 | 7485382 | These cells displayed evidence of immune activation with expression of receptors for interleukin-2 (IL-2R) plus Th1 cytokines; dense labeling for IFN-gamma and tumor necrosis factor-alpha, plus lesser amounts of IL-2, was observed. |
| 25 | 7485382 | MNC lacked labeling for IL-4, IL-10, prostaglandin-E, or transforming growth factor-beta. |
| 26 | 7485382 | By contrast, at 10 weeks, pancreatic tissues from NOD mice fed insulin showed considerably less insulitis, and the residual MNC, although still largely CD4+ T cells plus macrophages, showed dense labeling for IL-4, IL-10, prostaglandin-E, and transforming growth factor-beta and an absence of IL-2, IFN-gamma or tumor necrosis factor-alpha Taken together with our previous findings, these data indicate that oral administration of insulin affects the development of diabetes in NOD mice through the generation of cells that elaborate immunoregulatory cytokines within the target organ and shift the balance from a Th1 to a Th2 pattern of cytokine expression. |
| 27 | 7485382 | Suppression of insulitis in non-obese diabetic (NOD) mice by oral insulin administration is associated with selective expression of interleukin-4 and -10, transforming growth factor-beta, and prostaglandin-E. |
| 28 | 7485382 | Immunohistological studies using monoclonal antibodies showed that infiltrating MNC consisted mainly of CD4+ T cells ( > 75% of leukocytes) plus smaller numbers of macrophages and CD8+ T cells. |
| 29 | 7485382 | These cells displayed evidence of immune activation with expression of receptors for interleukin-2 (IL-2R) plus Th1 cytokines; dense labeling for IFN-gamma and tumor necrosis factor-alpha, plus lesser amounts of IL-2, was observed. |
| 30 | 7485382 | MNC lacked labeling for IL-4, IL-10, prostaglandin-E, or transforming growth factor-beta. |
| 31 | 7485382 | By contrast, at 10 weeks, pancreatic tissues from NOD mice fed insulin showed considerably less insulitis, and the residual MNC, although still largely CD4+ T cells plus macrophages, showed dense labeling for IL-4, IL-10, prostaglandin-E, and transforming growth factor-beta and an absence of IL-2, IFN-gamma or tumor necrosis factor-alpha Taken together with our previous findings, these data indicate that oral administration of insulin affects the development of diabetes in NOD mice through the generation of cells that elaborate immunoregulatory cytokines within the target organ and shift the balance from a Th1 to a Th2 pattern of cytokine expression. |
| 32 | 7485382 | Suppression of insulitis in non-obese diabetic (NOD) mice by oral insulin administration is associated with selective expression of interleukin-4 and -10, transforming growth factor-beta, and prostaglandin-E. |
| 33 | 7485382 | Immunohistological studies using monoclonal antibodies showed that infiltrating MNC consisted mainly of CD4+ T cells ( > 75% of leukocytes) plus smaller numbers of macrophages and CD8+ T cells. |
| 34 | 7485382 | These cells displayed evidence of immune activation with expression of receptors for interleukin-2 (IL-2R) plus Th1 cytokines; dense labeling for IFN-gamma and tumor necrosis factor-alpha, plus lesser amounts of IL-2, was observed. |
| 35 | 7485382 | MNC lacked labeling for IL-4, IL-10, prostaglandin-E, or transforming growth factor-beta. |
| 36 | 7485382 | By contrast, at 10 weeks, pancreatic tissues from NOD mice fed insulin showed considerably less insulitis, and the residual MNC, although still largely CD4+ T cells plus macrophages, showed dense labeling for IL-4, IL-10, prostaglandin-E, and transforming growth factor-beta and an absence of IL-2, IFN-gamma or tumor necrosis factor-alpha Taken together with our previous findings, these data indicate that oral administration of insulin affects the development of diabetes in NOD mice through the generation of cells that elaborate immunoregulatory cytokines within the target organ and shift the balance from a Th1 to a Th2 pattern of cytokine expression. |
| 37 | 7489754 | However, cytokine analysis of the response revealed important differences between NOD mice and their H-2E transgenic counterparts: H-2E expression was associated with reduced interleukin-4 secretion and enhanced interferon-gamma (IFN-gamma) secretion by lymph node cells, while the response of central nervous system infiltrating T cells displayed a markedly enhanced IFN-gamma response. |
| 38 | 7499194 | PTB domains of IRS-1 and Shc have distinct but overlapping binding specificities. |
| 39 | 7499194 | By serial truncation, we show that a 174-residue region of Shc p52 (33-206) has full PTB activity. |
| 40 | 7499194 | Phosphopeptide assays developed to compare PTB domain specificities show that the Shc PTB domain binds with highest affinity to psi XN beta 1 beta 2 pY motifs derived from middle T (mT), TrkA, ErbB4, or epidermal growth factor receptors (psi = hydrophobic, beta = beta-turn forming); the IRS-1 PTB domain does not bind with this motif. |
| 41 | 7499194 | In contrast, both the Shc and IRS-1 PTB domains bind psi psi psi XXN beta 1 beta 2pY sequences derived from insulin and interleukin 4 receptors, although specificities vary in detail. |
| 42 | 7499194 | Shc and IRS-1 are phosphorylated by distinct but overlapping sets of receptor-linked tyrosine kinases. |
| 43 | 7510100 | The stimulatory cytokines include interleukin-1 (IL-1), interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and migration inhibitory factor. |
| 44 | 7510100 | A number of cytokines, including IL-4, IL-10 and transforming growth factor-beta, can down regulate the induction of NO synthase in macrophages. |
| 45 | 7532600 | Cyclophosphamide treatment of female non-obese diabetic mice causes enhanced expression of inducible nitric oxide synthase and interferon-gamma, but not of interleukin-4. |
| 46 | 7532600 | In pancreatic lesions of non-obese diabetic (NOD) mice the expression of inducible nitric oxide synthase (iNOS) and of the cytokines interferon-gamma and interleukin-4 were studied. |
| 47 | 7532600 | The enhancement of iNOS after cyclophosphamide correlated with an increase of T-helper type 1 (Th1) associated interferon-gamma expression while T-helper type 2 (Th2) associated interleukin-4 was the dominant cytokine prior to cyclophosphamide and after diabetes onset. |
| 48 | 7532600 | Cyclophosphamide treatment of female non-obese diabetic mice causes enhanced expression of inducible nitric oxide synthase and interferon-gamma, but not of interleukin-4. |
| 49 | 7532600 | In pancreatic lesions of non-obese diabetic (NOD) mice the expression of inducible nitric oxide synthase (iNOS) and of the cytokines interferon-gamma and interleukin-4 were studied. |
| 50 | 7532600 | The enhancement of iNOS after cyclophosphamide correlated with an increase of T-helper type 1 (Th1) associated interferon-gamma expression while T-helper type 2 (Th2) associated interleukin-4 was the dominant cytokine prior to cyclophosphamide and after diabetes onset. |
| 51 | 7532600 | Cyclophosphamide treatment of female non-obese diabetic mice causes enhanced expression of inducible nitric oxide synthase and interferon-gamma, but not of interleukin-4. |
| 52 | 7532600 | In pancreatic lesions of non-obese diabetic (NOD) mice the expression of inducible nitric oxide synthase (iNOS) and of the cytokines interferon-gamma and interleukin-4 were studied. |
| 53 | 7532600 | The enhancement of iNOS after cyclophosphamide correlated with an increase of T-helper type 1 (Th1) associated interferon-gamma expression while T-helper type 2 (Th2) associated interleukin-4 was the dominant cytokine prior to cyclophosphamide and after diabetes onset. |
| 54 | 7537670 | Five clones produced interferon (IFN)-gamma but not interleukin (IL)-4, placing them in the T helper type 1 (TH1)-like category whereas one clone produced both IL-4 and IFN-gamma, a characteristic of TH0 cells. |
| 55 | 7540571 | We detect a significant increase in the level of expression of interferon (IFN)-alpha in the pancreases of the diabetic patients as compared with the control pancreases. |
| 56 | 7540571 | In contrast, IFN-beta was detected at comparable levels in both groups, while IFN-gamma was detected in three of four control pancreases and one of four pancreases from the diabetic individuals. |
| 57 | 7540571 | The IFN-alpha cDNAs generated by the RT-PCR were cloned and sequenced to determine which alpha-subtypes were being expressed. |
| 58 | 7540571 | We also examined these pancreases for the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-2, IL-4, and IL-6. |
| 59 | 7540571 | We found no detectable expression of TNF-alpha or IL-2 in any pancreases, and the expression of the other cytokines was variable, with no pattern emerging from the comparison of the diabetic and nondiabetic individuals. |
| 60 | 7540571 | We conclude that, of the cytokines examined, only IFN-alpha was significantly increased in the diabetic patients, a result that is consistent with the possibility that this cytokine is directly involved in the development of type I diabetes. |
| 61 | 7559579 | Insulin receptor substrate-1 (IRS-1) is the major cytoplasmic substrate of the insulin and insulin-like growth factor (IGF)-1 receptors. |
| 62 | 7559579 | Transgenic mice lacking IRS-1 are resistant to insulin and IGF-1, but exhibit significant residual insulin action which corresponds to the presence of an alternative high molecular weight substrate in liver and muscle. |
| 63 | 7559579 | F. (1995) Nature 377, 173-177) purified and cloned 4PS, the major substrate of the IL-4 receptor-associated tyrosine kinase in myeloid cells, which has significant structural similarity to IRS-1. |
| 64 | 7559579 | Following insulin stimulation, 4PS is rapidly phosphorylated in liver and muscle, binds to the p85 subunit of PI 3-kinase, and activates the enzyme. |
| 65 | 7559579 | IRS-2, which plays a major role in physiologic insulin signal transduction via both PI 3-kinase activation and Grb 2/Sos association. |
| 66 | 7559579 | In IRS-1-deficient mice, 4PS/IRS-2 provides signal transduction to these two major pathways of insulin signaling. |
| 67 | 7578887 | The percentage of CD4+PBL was higher in NOD/Smrf females than males, was intermediate in [NOD X NON] F1 mice and approximated a 1:1 distribution in F1 mice backcrossed to either NOD or NON parental strains, suggesting primary control of the phenotype by an incompletely dominant gene, but not excluding additional effects by other genes. |
| 68 | 7578887 | We term this primary gene Tlf(T lymphocyte frequency) because it also influenced the percentage of CD8+ T cells, although to lesser extent and independently from the MHC previously shown to lower the CD8+ T cell fraction in NON mice. |
| 69 | 7578887 | Dihydrotestosterone simultaneously lowered CD4+ PBL levels and prevented diabetes in NOD females while, in vitro, it had a differential effect on Con A elicited cytokines, increasing IL-2 22% and decreasing IL-4 39% (p < 0.0001). |
| 70 | 7640349 | Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1. |
| 71 | 7640349 | Cytokines, in particular interleukin 1 beta (IL-1 beta), have been implicated in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. |
| 72 | 7640349 | In the rat prolonged exposure in vitro of islets of IL-1 beta leads to nitric oxide formation, impaired glucose metabolism and inhibition of insulin secretion. |
| 73 | 7640349 | In the present study we have investigated the effect of IL-4 alone and in combination with IL-1 beta on islet cells. |
| 74 | 7640349 | For this purpose isolated rat pancreatic islets were cultured for 42 h in medium supplemented with 0, 0.1, 1.0 or 10 ng/ml of human IL-4 in the absence or presence of 25 U/ml of IL-1 beta during the last 24 h of culture. |
| 75 | 7640349 | IL-4 alone dose-dependently decreased the islet glucose oxidation rate and the glucose-stimulated insulin release. |
| 76 | 7640349 | Furthermore, the cytokine potentiated IL-1 beta-induced reduction in the islet DNA content and (pro)insulin biosynthesis rate. |
| 77 | 7640349 | The medium nitrite accumulation, as an index of nitric oxide formation, was not influenced by IL-4 (10 ng/ml) alone, whilst IL-1 beta stimulation of medium nitrite was partly reduced by IL-4. |
| 78 | 7640349 | Compared to the action exerted by IL-1 beta the inhibitory action of IL-4 on rat islet function was moderate, and the latter action seems to be independent on nitric oxide production. |
| 79 | 7640349 | Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1. |
| 80 | 7640349 | Cytokines, in particular interleukin 1 beta (IL-1 beta), have been implicated in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. |
| 81 | 7640349 | In the rat prolonged exposure in vitro of islets of IL-1 beta leads to nitric oxide formation, impaired glucose metabolism and inhibition of insulin secretion. |
| 82 | 7640349 | In the present study we have investigated the effect of IL-4 alone and in combination with IL-1 beta on islet cells. |
| 83 | 7640349 | For this purpose isolated rat pancreatic islets were cultured for 42 h in medium supplemented with 0, 0.1, 1.0 or 10 ng/ml of human IL-4 in the absence or presence of 25 U/ml of IL-1 beta during the last 24 h of culture. |
| 84 | 7640349 | IL-4 alone dose-dependently decreased the islet glucose oxidation rate and the glucose-stimulated insulin release. |
| 85 | 7640349 | Furthermore, the cytokine potentiated IL-1 beta-induced reduction in the islet DNA content and (pro)insulin biosynthesis rate. |
| 86 | 7640349 | The medium nitrite accumulation, as an index of nitric oxide formation, was not influenced by IL-4 (10 ng/ml) alone, whilst IL-1 beta stimulation of medium nitrite was partly reduced by IL-4. |
| 87 | 7640349 | Compared to the action exerted by IL-1 beta the inhibitory action of IL-4 on rat islet function was moderate, and the latter action seems to be independent on nitric oxide production. |
| 88 | 7640349 | Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1. |
| 89 | 7640349 | Cytokines, in particular interleukin 1 beta (IL-1 beta), have been implicated in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. |
| 90 | 7640349 | In the rat prolonged exposure in vitro of islets of IL-1 beta leads to nitric oxide formation, impaired glucose metabolism and inhibition of insulin secretion. |
| 91 | 7640349 | In the present study we have investigated the effect of IL-4 alone and in combination with IL-1 beta on islet cells. |
| 92 | 7640349 | For this purpose isolated rat pancreatic islets were cultured for 42 h in medium supplemented with 0, 0.1, 1.0 or 10 ng/ml of human IL-4 in the absence or presence of 25 U/ml of IL-1 beta during the last 24 h of culture. |
| 93 | 7640349 | IL-4 alone dose-dependently decreased the islet glucose oxidation rate and the glucose-stimulated insulin release. |
| 94 | 7640349 | Furthermore, the cytokine potentiated IL-1 beta-induced reduction in the islet DNA content and (pro)insulin biosynthesis rate. |
| 95 | 7640349 | The medium nitrite accumulation, as an index of nitric oxide formation, was not influenced by IL-4 (10 ng/ml) alone, whilst IL-1 beta stimulation of medium nitrite was partly reduced by IL-4. |
| 96 | 7640349 | Compared to the action exerted by IL-1 beta the inhibitory action of IL-4 on rat islet function was moderate, and the latter action seems to be independent on nitric oxide production. |
| 97 | 7640349 | Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1. |
| 98 | 7640349 | Cytokines, in particular interleukin 1 beta (IL-1 beta), have been implicated in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. |
| 99 | 7640349 | In the rat prolonged exposure in vitro of islets of IL-1 beta leads to nitric oxide formation, impaired glucose metabolism and inhibition of insulin secretion. |
| 100 | 7640349 | In the present study we have investigated the effect of IL-4 alone and in combination with IL-1 beta on islet cells. |
| 101 | 7640349 | For this purpose isolated rat pancreatic islets were cultured for 42 h in medium supplemented with 0, 0.1, 1.0 or 10 ng/ml of human IL-4 in the absence or presence of 25 U/ml of IL-1 beta during the last 24 h of culture. |
| 102 | 7640349 | IL-4 alone dose-dependently decreased the islet glucose oxidation rate and the glucose-stimulated insulin release. |
| 103 | 7640349 | Furthermore, the cytokine potentiated IL-1 beta-induced reduction in the islet DNA content and (pro)insulin biosynthesis rate. |
| 104 | 7640349 | The medium nitrite accumulation, as an index of nitric oxide formation, was not influenced by IL-4 (10 ng/ml) alone, whilst IL-1 beta stimulation of medium nitrite was partly reduced by IL-4. |
| 105 | 7640349 | Compared to the action exerted by IL-1 beta the inhibitory action of IL-4 on rat islet function was moderate, and the latter action seems to be independent on nitric oxide production. |
| 106 | 7640349 | Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1. |
| 107 | 7640349 | Cytokines, in particular interleukin 1 beta (IL-1 beta), have been implicated in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. |
| 108 | 7640349 | In the rat prolonged exposure in vitro of islets of IL-1 beta leads to nitric oxide formation, impaired glucose metabolism and inhibition of insulin secretion. |
| 109 | 7640349 | In the present study we have investigated the effect of IL-4 alone and in combination with IL-1 beta on islet cells. |
| 110 | 7640349 | For this purpose isolated rat pancreatic islets were cultured for 42 h in medium supplemented with 0, 0.1, 1.0 or 10 ng/ml of human IL-4 in the absence or presence of 25 U/ml of IL-1 beta during the last 24 h of culture. |
| 111 | 7640349 | IL-4 alone dose-dependently decreased the islet glucose oxidation rate and the glucose-stimulated insulin release. |
| 112 | 7640349 | Furthermore, the cytokine potentiated IL-1 beta-induced reduction in the islet DNA content and (pro)insulin biosynthesis rate. |
| 113 | 7640349 | The medium nitrite accumulation, as an index of nitric oxide formation, was not influenced by IL-4 (10 ng/ml) alone, whilst IL-1 beta stimulation of medium nitrite was partly reduced by IL-4. |
| 114 | 7640349 | Compared to the action exerted by IL-1 beta the inhibitory action of IL-4 on rat islet function was moderate, and the latter action seems to be independent on nitric oxide production. |
| 115 | 7640349 | Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1. |
| 116 | 7640349 | Cytokines, in particular interleukin 1 beta (IL-1 beta), have been implicated in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. |
| 117 | 7640349 | In the rat prolonged exposure in vitro of islets of IL-1 beta leads to nitric oxide formation, impaired glucose metabolism and inhibition of insulin secretion. |
| 118 | 7640349 | In the present study we have investigated the effect of IL-4 alone and in combination with IL-1 beta on islet cells. |
| 119 | 7640349 | For this purpose isolated rat pancreatic islets were cultured for 42 h in medium supplemented with 0, 0.1, 1.0 or 10 ng/ml of human IL-4 in the absence or presence of 25 U/ml of IL-1 beta during the last 24 h of culture. |
| 120 | 7640349 | IL-4 alone dose-dependently decreased the islet glucose oxidation rate and the glucose-stimulated insulin release. |
| 121 | 7640349 | Furthermore, the cytokine potentiated IL-1 beta-induced reduction in the islet DNA content and (pro)insulin biosynthesis rate. |
| 122 | 7640349 | The medium nitrite accumulation, as an index of nitric oxide formation, was not influenced by IL-4 (10 ng/ml) alone, whilst IL-1 beta stimulation of medium nitrite was partly reduced by IL-4. |
| 123 | 7640349 | Compared to the action exerted by IL-1 beta the inhibitory action of IL-4 on rat islet function was moderate, and the latter action seems to be independent on nitric oxide production. |
| 124 | 7652767 | Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. |
| 125 | 7652767 | IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. |
| 126 | 7652767 | In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. |
| 127 | 7652767 | Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. |
| 128 | 7652767 | Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. |
| 129 | 7652767 | Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. |
| 130 | 7652767 | Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. |
| 131 | 7652767 | These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts. |
| 132 | 7652767 | Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. |
| 133 | 7652767 | IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. |
| 134 | 7652767 | In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. |
| 135 | 7652767 | Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. |
| 136 | 7652767 | Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. |
| 137 | 7652767 | Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. |
| 138 | 7652767 | Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. |
| 139 | 7652767 | These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts. |
| 140 | 7652767 | Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. |
| 141 | 7652767 | IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. |
| 142 | 7652767 | In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. |
| 143 | 7652767 | Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. |
| 144 | 7652767 | Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. |
| 145 | 7652767 | Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. |
| 146 | 7652767 | Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. |
| 147 | 7652767 | These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts. |
| 148 | 7652767 | Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. |
| 149 | 7652767 | IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. |
| 150 | 7652767 | In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. |
| 151 | 7652767 | Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. |
| 152 | 7652767 | Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. |
| 153 | 7652767 | Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. |
| 154 | 7652767 | Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. |
| 155 | 7652767 | These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts. |
| 156 | 7652767 | Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. |
| 157 | 7652767 | IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. |
| 158 | 7652767 | In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. |
| 159 | 7652767 | Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. |
| 160 | 7652767 | Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. |
| 161 | 7652767 | Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. |
| 162 | 7652767 | Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. |
| 163 | 7652767 | These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts. |
| 164 | 7652767 | Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. |
| 165 | 7652767 | IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. |
| 166 | 7652767 | In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. |
| 167 | 7652767 | Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. |
| 168 | 7652767 | Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. |
| 169 | 7652767 | Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. |
| 170 | 7652767 | Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. |
| 171 | 7652767 | These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts. |
| 172 | 7652767 | Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. |
| 173 | 7652767 | IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. |
| 174 | 7652767 | In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. |
| 175 | 7652767 | Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. |
| 176 | 7652767 | Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. |
| 177 | 7652767 | Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. |
| 178 | 7652767 | Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. |
| 179 | 7652767 | These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts. |
| 180 | 7652767 | Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. |
| 181 | 7652767 | IL-4 and IL-10 are cytokines that inhibit cell-mediated immunity. |
| 182 | 7652767 | In this study, we evaluated the effects of IL-4 and IL-10 on the survival of syngeneic pancreatic islets transplanted into diabetic NOD mice. |
| 183 | 7652767 | Islet grafts survived beyond 18 days and normoglycemia was maintained in 67% (10 of 15) of mice treated with IL-4 plus IL-10, but in none (0 of 20) of vehicle-injected (control) mice. |
| 184 | 7652767 | Also, 40% (6 of 15) of the mice treated with IL-4 plus IL-10 were normoglycemic at 30 days after transplantation, compared with 14% (1 of 7) of the mice treated with IL-4 alone, 8% (1 of 13) of the mice treated with IL-10 alone, and none (0 of 20) of the control mice. |
| 185 | 7652767 | Histological examination of grafts at 10 days after transplantation revealed peri-islet accumulations of mononuclear leukocytes and intact islet beta cells in grafts from IL-4 plus IL-10-treated mice, whereas islets were infiltrated by leukocytes and the beta cell mass was greatly reduced in grafts from control mice. |
| 186 | 7652767 | Polymerase chain reaction (PCR) analysis of cytokine mRNA expression in the grafts revealed higher levels of IL-2, IFN gamma, and IL-10 mRNA in grafts of diabetic compared with normoglycemic control mice, whereas IFN gamma and TNF alpha mRNA levels were significantly decreased in grafts of IL-4 plus IL-10-treated mice compared with either normoglycemic or diabetic control mice. |
| 187 | 7652767 | These results suggest that T helper (Th)1 cells and their cytokine products (IL-2, IFN gamma, and TNF alpha) may promote islet beta cell destructive insulitis and autoimmune diabetes recurrence in syngeneic islet-transplanted NOD mice, and that administration of IL-4 plus IL-10 may inhibit diabetes recurrence by suppressing Th1 cytokine production in the islet grafts. |
| 188 | 7667243 | These responses were associated with a marked increase in splenocyte interleukin-4 (IL-4) production, a reduction in interferon-gamma production, and a down-regulation of CD45RB isoform expression. |
| 189 | 7667243 | Macrophages in the EFAD group exerted a reduced suppressive effect on concanavalin A-induced splenocyte proliferation and were found to release increased amounts of tumor necrosis factor-alpha and IL-1 and reduced amounts of prostaglandin E2. |
| 190 | 7675087 | Role of IRS-2 in insulin and cytokine signalling. |
| 191 | 7675087 | The protein IRS-1 acts as an interface between signalling proteins with Src-homology-2 domains (SH2 proteins) and the receptors for insulin, IGF-1, growth hormone, several interleukins (IL-4, IL-9, IL-13) and other cytokines. |
| 192 | 7675087 | We purified and cloned a likely candidate called 4PS from myeloid progenitor cells and, because of its resemblance to IRS-1, we designate it IRS-2. |
| 193 | 7675087 | Alignment of the sequences of IRS-2 and IRS-1 revealed a highly conserved amino terminus containing a pleckstrin-homology domain and a phosphotyrosine-binding domain, and a poorly conserved carboxy terminus containing several tyrosine phosphorylation motifs. |
| 194 | 7718517 | Differential patterns of production of granulocyte macrophage colony stimulating factor, IL-2, IL-3 and IL-4 by cultured islets of Langerhans from non-obese diabetic and non-diabetic strains of mice. |
| 195 | 7718517 | Each of the cytokines studied, i.e. granulocyte-monocyte colony stimulating factor (GM-CSF), IL-2, IL-3 and IL-4, showed different patterns of production. |
| 196 | 7718517 | For NOD islets, GM-CSF and IL-3 levels correlated with the degree of infiltrate release, although production was not confined to islets that released mononuclear cells in vitro. |
| 197 | 7718517 | However, GM-CSF differed from IL-3 in that it was produced by islets from some non-diabetic strains of mice, whereas IL-3 production was confined to NOD islets. |
| 198 | 7718517 | Finally, male NOD islets produced more IL-4 than females, possibly related to the lower incidence of diabetes in males, but unlike GM-CSF and IL-3, IL-4 production did not correlate with the degree of infiltrate released in culture. |
| 199 | 7718517 | Differential patterns of production of granulocyte macrophage colony stimulating factor, IL-2, IL-3 and IL-4 by cultured islets of Langerhans from non-obese diabetic and non-diabetic strains of mice. |
| 200 | 7718517 | Each of the cytokines studied, i.e. granulocyte-monocyte colony stimulating factor (GM-CSF), IL-2, IL-3 and IL-4, showed different patterns of production. |
| 201 | 7718517 | For NOD islets, GM-CSF and IL-3 levels correlated with the degree of infiltrate release, although production was not confined to islets that released mononuclear cells in vitro. |
| 202 | 7718517 | However, GM-CSF differed from IL-3 in that it was produced by islets from some non-diabetic strains of mice, whereas IL-3 production was confined to NOD islets. |
| 203 | 7718517 | Finally, male NOD islets produced more IL-4 than females, possibly related to the lower incidence of diabetes in males, but unlike GM-CSF and IL-3, IL-4 production did not correlate with the degree of infiltrate released in culture. |
| 204 | 7718517 | Differential patterns of production of granulocyte macrophage colony stimulating factor, IL-2, IL-3 and IL-4 by cultured islets of Langerhans from non-obese diabetic and non-diabetic strains of mice. |
| 205 | 7718517 | Each of the cytokines studied, i.e. granulocyte-monocyte colony stimulating factor (GM-CSF), IL-2, IL-3 and IL-4, showed different patterns of production. |
| 206 | 7718517 | For NOD islets, GM-CSF and IL-3 levels correlated with the degree of infiltrate release, although production was not confined to islets that released mononuclear cells in vitro. |
| 207 | 7718517 | However, GM-CSF differed from IL-3 in that it was produced by islets from some non-diabetic strains of mice, whereas IL-3 production was confined to NOD islets. |
| 208 | 7718517 | Finally, male NOD islets produced more IL-4 than females, possibly related to the lower incidence of diabetes in males, but unlike GM-CSF and IL-3, IL-4 production did not correlate with the degree of infiltrate released in culture. |
| 209 | 7722337 | We found that mRNA levels of IL-1 beta, IL-2, IL-4, IL-10, and IFN-gamma in mononuclear cells from islets of diabetes-prone female NOD mice increased progressively as these cells infiltrated the islets from age 5 wk to diabetes onset (> 13 wk). |
| 210 | 7722337 | Splenic cell mRNA levels of IFN-gamma and IL-4 were not different in the four groups of mice. |
| 211 | 7722337 | We found that mRNA levels of IL-1 beta, IL-2, IL-4, IL-10, and IFN-gamma in mononuclear cells from islets of diabetes-prone female NOD mice increased progressively as these cells infiltrated the islets from age 5 wk to diabetes onset (> 13 wk). |
| 212 | 7722337 | Splenic cell mRNA levels of IFN-gamma and IL-4 were not different in the four groups of mice. |
| 213 | 7836934 | T cells play a major role in the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. |
| 214 | 7836934 | Administration of interleukin 12 (IL-12), a key cytokine which guides the development of T helper type 1 (Th1) CD4+ T cells, induces rapid onset of IDDM in NOD, but not in BALB/c mice. |
| 215 | 7836934 | CD4+ pancreas-infiltrating T cells, after activation by insolubilized anti T cell receptor antibody, secrete high levels of interferon gamma and low levels of IL-4. |
| 216 | 7836934 | Therefore, IL-12 administration accelerates IDDM development in genetically susceptible NOD mice, and this correlates with increased Th1 cytokine production by islet-infiltrating cells. |
| 217 | 7869038 | Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C-mediated pathways for cytokine gene transcription in human T cells. |
| 218 | 7869038 | Engagement of the T cell receptor for antigen activates phospholipase C resulting in an increase in intracellular free calcium concentration ([Ca2+]i) and activation of protein kinase C (PKC). |
| 219 | 7869038 | Recent studies have identified calcineurin as a key enzyme for interleukin (IL)-2 and IL-4 promoter activation. |
| 220 | 7869038 | The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways. |
| 221 | 7869038 | Similar results were obtained when a construct containing the IL-4 promoter also was used. gamma B*CaM-K also downregulated the activation of AP-1 in response to transfection with a constitutively active mutant of PKC or stimulation with PMA. |
| 222 | 7869038 | Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C-mediated pathways for cytokine gene transcription in human T cells. |
| 223 | 7869038 | Engagement of the T cell receptor for antigen activates phospholipase C resulting in an increase in intracellular free calcium concentration ([Ca2+]i) and activation of protein kinase C (PKC). |
| 224 | 7869038 | Recent studies have identified calcineurin as a key enzyme for interleukin (IL)-2 and IL-4 promoter activation. |
| 225 | 7869038 | The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways. |
| 226 | 7869038 | Similar results were obtained when a construct containing the IL-4 promoter also was used. gamma B*CaM-K also downregulated the activation of AP-1 in response to transfection with a constitutively active mutant of PKC or stimulation with PMA. |
| 227 | 7888039 | The response was directed to the same peptide and most were found to produce IFN gamma, but none produced IL-4. |
| 228 | 7913115 | Insulin-dependent diabetes mellitus (IDDM), in which only the pancreatic beta cells are destroyed by the autoimmune response, is the paradigm of organ-specific autoimmunity. |
| 229 | 7913115 | The analysis of the correlation between class I overexpression, residual insulin, and insulitis suggests that the first event is the increase of HLA class I expression. |
| 230 | 7913115 | Of adhesion molecules, ICAM-1, VLA, VCAM, and LFA-3 were normal and only ICAM-1 was moderately overexpressed in and around the islets of case 1 insulitis, as was detected by immunofluorescence which showed that 18% of the islets of case 1 had CD8+ lymphocytes as the predominant population. |
| 231 | 7913115 | Reverse transcription-PCR demonstrated moderate V beta skewing and the profile of cytokines expected in CTLs: IL-2, IL-4, IL-10, and IFN-gamma negative, perforin positive. |
| 232 | 7913115 | In addition, IFN-alpha, IFN-beta, and IL-6 transcripts were detected in the case 1 pancreas, consistent with the existence of a silent viral infection. |
| 233 | 7961833 | Insulin receptor substrate-1 mediates phosphatidylinositol 3'-kinase and p70S6k signaling during insulin, insulin-like growth factor-1, and interleukin-4 stimulation. |
| 234 | 7961833 | Insulin Receptor Substrate-1 (IRS-1) is an endogenous cellular protein that is tyrosine phosphorylated during stimulation of cells with insulin, IGF-1, and interleukin 4 (IL-4). |
| 235 | 7961833 | The 32D myeloid progenitor cell line contains few insulin receptors and no detectable IRS-1. |
| 236 | 7961833 | Expression of the insulin receptor alone partially mediates insulin-stimulated microtubule-associated protein (MAP) kinase activation, and the addition of IRS-1 enhances this effect (Myers, M. |
| 237 | 7961833 | Expression of IRS-1 alone in 32D cells mediates the stimulation of p70S6k by insulin, IGF-1, or IL-4; addition of insulin receptor to these cells increases the sensitivity of the insulin response. |
| 238 | 7961833 | In contrast, full insulin stimulation of PI 3'-kinase requires both the insulin receptor and IRS-1, suggesting that a high level of IRS-1 phosphorylation is required for insulin-stimulated PI 3'-kinase activation, whereas a low level of IRS-1 tyrosine phosphorylation transmits an essential signal to p70S6k. |
| 239 | 7961833 | Both insulin receptors and IRS-1 are required for mitogenic signaling in 32D cells suggesting that MAP kinase or p70S6k alone are not sufficient, and that both or additional unknown IRS-1-mediated signals are necessary. |
| 240 | 7961833 | Insulin receptor substrate-1 mediates phosphatidylinositol 3'-kinase and p70S6k signaling during insulin, insulin-like growth factor-1, and interleukin-4 stimulation. |
| 241 | 7961833 | Insulin Receptor Substrate-1 (IRS-1) is an endogenous cellular protein that is tyrosine phosphorylated during stimulation of cells with insulin, IGF-1, and interleukin 4 (IL-4). |
| 242 | 7961833 | The 32D myeloid progenitor cell line contains few insulin receptors and no detectable IRS-1. |
| 243 | 7961833 | Expression of the insulin receptor alone partially mediates insulin-stimulated microtubule-associated protein (MAP) kinase activation, and the addition of IRS-1 enhances this effect (Myers, M. |
| 244 | 7961833 | Expression of IRS-1 alone in 32D cells mediates the stimulation of p70S6k by insulin, IGF-1, or IL-4; addition of insulin receptor to these cells increases the sensitivity of the insulin response. |
| 245 | 7961833 | In contrast, full insulin stimulation of PI 3'-kinase requires both the insulin receptor and IRS-1, suggesting that a high level of IRS-1 phosphorylation is required for insulin-stimulated PI 3'-kinase activation, whereas a low level of IRS-1 tyrosine phosphorylation transmits an essential signal to p70S6k. |
| 246 | 7961833 | Both insulin receptors and IRS-1 are required for mitogenic signaling in 32D cells suggesting that MAP kinase or p70S6k alone are not sufficient, and that both or additional unknown IRS-1-mediated signals are necessary. |
| 247 | 7961833 | Insulin receptor substrate-1 mediates phosphatidylinositol 3'-kinase and p70S6k signaling during insulin, insulin-like growth factor-1, and interleukin-4 stimulation. |
| 248 | 7961833 | Insulin Receptor Substrate-1 (IRS-1) is an endogenous cellular protein that is tyrosine phosphorylated during stimulation of cells with insulin, IGF-1, and interleukin 4 (IL-4). |
| 249 | 7961833 | The 32D myeloid progenitor cell line contains few insulin receptors and no detectable IRS-1. |
| 250 | 7961833 | Expression of the insulin receptor alone partially mediates insulin-stimulated microtubule-associated protein (MAP) kinase activation, and the addition of IRS-1 enhances this effect (Myers, M. |
| 251 | 7961833 | Expression of IRS-1 alone in 32D cells mediates the stimulation of p70S6k by insulin, IGF-1, or IL-4; addition of insulin receptor to these cells increases the sensitivity of the insulin response. |
| 252 | 7961833 | In contrast, full insulin stimulation of PI 3'-kinase requires both the insulin receptor and IRS-1, suggesting that a high level of IRS-1 phosphorylation is required for insulin-stimulated PI 3'-kinase activation, whereas a low level of IRS-1 tyrosine phosphorylation transmits an essential signal to p70S6k. |
| 253 | 7961833 | Both insulin receptors and IRS-1 are required for mitogenic signaling in 32D cells suggesting that MAP kinase or p70S6k alone are not sufficient, and that both or additional unknown IRS-1-mediated signals are necessary. |
| 254 | 7988786 | Analysis of cytokine mRNA expression in syngeneic islet grafts of NOD mice: interleukin 2 and interferon gamma mRNA expression correlate with graft rejection and interleukin 10 with graft survival. |
| 255 | 7988786 | Interleukin 10 mRNA expression was significantly increased whereas interleukin 2 and interferon gamma mRNA levels were significantly decreased in islet grafts from complete Freund's adjuvant-injected mice compared to control mice. |
| 256 | 7988786 | Levels of mRNA for interleukin 1 beta, interleukin 4, and tumour necrosis factor alpha were not significantly different in islet grafts from complete Freund's adjuvant-injected and control mice. |
| 257 | 7988786 | These findings suggest that a Th1 subset of lymphocytes and their cytokine products, interleukin 2 and interferon gamma, may be involved in the rejection of syngeneic islet grafts and diabetes recurrence in NOD mice, and that the protective effect of complete Freund's adjuvant may result from the induction of interleukin 10 production and consequent down-regulation of Th1 cells and cytokines in the islet graft. |
| 258 | 8011155 | Suppression can be adoptively transferred by CD8+ T lymphocytes which act by releasing TGF-beta and IL-4 following antigen-specific triggering. |
| 259 | 8048169 | Insulin-receptor substrate 1 (IRS-1) is a principal substrate of the receptor tyrosine kinase for insulin and insulin-like growth factor 1, and a substrate for a tyrosine kinase activated by interleukin 4. |
| 260 | 8048169 | IRS-1 undergoes multisite tyrosine phosphorylation and mediates downstream signals by 'docking' various proteins that contain Src homology 2 domains. |
| 261 | 8056185 | In IDDM, IL-2 production by CD4-positive T lymphocytes within the IL-2 system is thought to be selectively defective. |
| 262 | 8056185 | On the other hand, IL-4, which is also produced by CD4-positive T lymphocytes, was increased. |
| 263 | 8056185 | Since IL-4 did not suppress IL-2 production, it would seem that the IL-2 producing subset in CD4+HLA-DR+ T cells is decreased in IDDM. |
| 264 | 8056185 | These results suggest that in recent onset IDDM, IL-2 receptor-positive circulating T cells require an IL-2 supply. |
| 265 | 8056185 | In IDDM, IL-2 production by CD4-positive T lymphocytes within the IL-2 system is thought to be selectively defective. |
| 266 | 8056185 | On the other hand, IL-4, which is also produced by CD4-positive T lymphocytes, was increased. |
| 267 | 8056185 | Since IL-4 did not suppress IL-2 production, it would seem that the IL-2 producing subset in CD4+HLA-DR+ T cells is decreased in IDDM. |
| 268 | 8056185 | These results suggest that in recent onset IDDM, IL-2 receptor-positive circulating T cells require an IL-2 supply. |
| 269 | 8094734 | Diabetes in these lymphopoenic rats was associated with extensive insulitis involving CD4+ and CD8+ T cells and macrophages. |
| 270 | 8094734 | The autoimmune diabetes and insulitis were completely prevented by the injection of a particular CD4+ T cell subset, isolated from healthy syngeneic donors, of the phenotype CD45RClow T cell receptor alpha/beta+ RT6+ Thy-1- OX-40-. |
| 271 | 8094734 | Cells of this protective phenotype, which make up about 5% of thoracic duct lymphocytes, were found to provide help for secondary antibody responses and produce interleukin 2 (IL-2) and IL-4, but no interferon gamma, on in vitro activation. |
| 272 | 8100786 | The NOD mouse may have as many as 10 susceptibility genes, including its novel IA major histocompatibility complex antigen and a defective interferon-gamma receptor, whereas human IDDM is so far known to be encoded by cis and trans complementation products of certain DQ genes on chromosome 6q, and a gene in the insulin-like growth factor II region on chromosome 11p. |
| 273 | 8100786 | Islet cell antibody negative siblings of IDDM patients appear to have lower than expected abilities to secrete insulin in response to intravenous glucose. |
| 274 | 8100786 | Sera from patients before and/or after developing IDDM immunoprecipitate two native proteins of 64,000- and 38,000-M(r) glutamic acid decarboxylase (GAD65) reacting to conformational epitopes. |
| 275 | 8100786 | It can be induced by as disparate means as tuberculin antigen administration, by interleukin-4 treatments, by transfer of T-cell lines generated in autologous mixed lymphocyte responses, and by immunization to insulin B-chain, whereas oral islet cell antigens, such as insulin, can delay diabetes onset in the NOD mouse. |
| 276 | 8102088 | Progressive disease was found to be associated with the presence in the serum of IgA, IgE, and IgG1 Candida-reactive specific antibodies, absent footpad reactions, and elevated production in vitro of the Th2 cytokines IL-4, IL-6, and IL-10 but not the Th1 cytokine IFN-gamma. |
| 277 | 8102088 | Both the Th2 and Th1 (IL-2 and IFN-gamma) cytokines were produced in vitro by CD4+ lymphocytes from noninfected diabetic mice that, in addition, showed a noticeable footpad reaction to Candida antigens. |
| 278 | 8105989 | Results indicate that 1) cytokine mRNA profiles exhibited by islet-infiltrating cells of female and male NOD mice were quite similar with the exception of IL-6 expression and the marked differences in the levels of IL-2 receptor and IL-1 alpha mRNA, 2) CD4+ T lymphocytes expressed IL-4, presumably IL-5, and occasionally IL-10 mRNA but no detectable IL-2 mRNA, 3) CD8+ T lymphocytes exhibited TNF-beta, perforin and high levels of IFN-gamma, and 4) IL-7 was expressed in the islet at very high levels. |
| 279 | 8168635 | The autoimmune response that leads to destruction of pancreatic islet beta-cells and insulin-dependent diabetes mellitus (IDDM) has a genetic basis; however, environmental factors can exert profound modulating effects on the genetic predisposition to this autoimmune response. |
| 280 | 8168635 | Thus, recent studies in NOD mice suggest that the islet beta-cell-directed autoimmune response may be mediated by a T-helper 1 (Th1) subset of T-cells producing the cytokines interleukin-2 (IL-2) and interferon-gamma. |
| 281 | 8168635 | These studies also suggest that the diabetes-protective effects of administering microbial agents, adjuvants, and a beta-cell autoantigen (GAD65 [glutamic acid decarboxylase]) may result from activation of a Th2 subset of T-cells that produce the cytokines IL-4 and IL-10 and consequently downregulate the Th1-cell-mediated autoimmune response. |
| 282 | 8181185 | In these studies the effect of IL-10 was determined on three parameters of diabetes: The development of hyperglycemia, the development of insulitis, and the production of insulin by beta cells. |
| 283 | 8181185 | These results indicated that monoclonal anti-IFN-gamma antibody greatly reduced the incidence of hyperglycemia in female NOD mice, while anti-IL-4, IL-5, and IL-10 were ineffective. |
| 284 | 8181185 | In subsequent studies, daily subcutaneous administration of IL-10, a known potent inhibitor of IFN-gamma production by TH1 T cells, to 9 and 10-week-old NODs was shown to delay the onset of disease and significantly reduce the incidence of diabetes. |
| 285 | 8181185 | Histopathology performed on pancreatic tissue demonstrated that treatment with IL-10 reduced the severity of insulitis, prevented cellular infiltration of islet cells, and promoted normal insulin production by beta cells. |
| 286 | 8193539 | IRS-1 is a principal substrate of the insulin receptor tyrosine kinase. |
| 287 | 8193539 | Interleukin-4 also stimulates IRS-1 phosphorylation, and it is suspected that a few more growth factors or cytokines will be added to form a select group of receptors that utilize the IRS-1 signaling pathway. |
| 288 | 8315397 | Beginning at the time of insulitis (7 wk of age), CD4+ and CD8+ mature thymocytes from nonobese diabetic (NOD) mice exhibit a proliferative unresponsiveness in vitro after T cell receptor (TCR) crosslinking. |
| 289 | 8315397 | However, since equivalent levels of IL-3 were secreted by Con A-activated NOD and BALB/c thymocytes, the unresponsiveness of NOD thymic T cells does not appear to be dependent on reduced IL-2 secretion. |
| 290 | 8315397 | Exogenous recombinant (r)IL-2 only partially reverses NOD thymocyte proliferative unresponsiveness to anti-CD3, and this is mediated by the inability of IL-2 to stimulate a complete IL-4 secretion response. |
| 291 | 8315397 | In contrast, exogenous IL-4 reverses the unresponsiveness of both NOD thymic and peripheral T cells completely, and this is associated with the complete restoration of an IL-2 secretion response. |
| 292 | 8315397 | Beginning at the time of insulitis (7 wk of age), CD4+ and CD8+ mature thymocytes from nonobese diabetic (NOD) mice exhibit a proliferative unresponsiveness in vitro after T cell receptor (TCR) crosslinking. |
| 293 | 8315397 | However, since equivalent levels of IL-3 were secreted by Con A-activated NOD and BALB/c thymocytes, the unresponsiveness of NOD thymic T cells does not appear to be dependent on reduced IL-2 secretion. |
| 294 | 8315397 | Exogenous recombinant (r)IL-2 only partially reverses NOD thymocyte proliferative unresponsiveness to anti-CD3, and this is mediated by the inability of IL-2 to stimulate a complete IL-4 secretion response. |
| 295 | 8315397 | In contrast, exogenous IL-4 reverses the unresponsiveness of both NOD thymic and peripheral T cells completely, and this is associated with the complete restoration of an IL-2 secretion response. |
| 296 | 8329398 | Comparison of the NMR structure of IL-4 with the X-ray structures of two other related proteins, granulocyte-macrophage colony stimulating factor [Diedrichs, K., Boone, T., & Karplus, P. |
| 297 | 8340230 | Mononuclear cells obtained from a child at the acute presentation of type I diabetes were stimulated in vitro with human insulin followed by IL-2 and IL-4. |
| 298 | 8405738 | In response to NOD antigen presenting cells, C2 cells secreted interferon-gamma, tumour necrosis factor-alpha and interleukin-6 but no detectable interleukin-2, interleukin-4 or interleukin-10, a pattern of cytokine secretion more characteristic of Th1 CD4 cells. |
| 299 | 8522063 | CD45RB(low) CD4+ splenocytes from diabetic NOD mice were transferred along with CD8+ splenocytes from diabetic mice into NOD-scid recipients, and all of the recipients became diabetic within 5 weeks posttransfer. |
| 300 | 8522063 | In contrast, no recipients (0 of 10) of CD45RB(high) CD4+ cells along with CD8+ splenocytes from diabetic mice became diabetic within 5 weeks posttransfer (P < 0.001). |
| 301 | 8522063 | CD45RB(low) CD4+ cells from diabetic mice showed a significantly higher ratio (approximately fivefold) of gamma-interferon (IFN-gamma) to interleukin (IL)-4 when compared with CD45RB(low) CD4+ cells from nondiabetic mice (P < 0.001). |
| 302 | 8558012 | IFN-gamma and IL-12p40 mRNA increase with age in both diabetic and insulin-treated nondiabetic BB rats. |
| 303 | 8558012 | In both DP and RT6-depleted DR rats, IFN-gamma mRNA was present in islets before and during disease onset. |
| 304 | 8558012 | IL-2 and IL-4 mRNAs were minimal or undetectable in infiltrated islets but present in activated peripheral T cells. |
| 305 | 8558012 | Similar cytokine mRNA profiles were observed in the thyroids of RT6-depleted DR rats and in the islets of DP rats treated with prophylactic parenteral insulin to prevent diabetes. |
| 306 | 8558012 | We conclude that IFN-gamma and IL-12 may play a major role in the expression of insulitis and thyroiditis in the BB rat, that Th1 lymphocytes may predominate over Th2 lymphocytes in these inflammatory lesions, and that prevention of diabetes by insulin is not associated with an alteration in the cytokine gene profile of islet infiltrating cells. |
| 307 | 8599837 | Transfection of a deletion mutant of the calcineurin catalytic subunit (delta CaM-AI) known to have Ca2+-independent, constitutive phosphatase activity increased IL-4 promoter activity by approximately 14-fold. |
| 308 | 8617981 | We have found that IL-2, IL-4, TNF-alpha, and IFN-gamma are expressed by the time the fourth dose of STZ is given. |
| 309 | 8617981 | However, expression of IFN-gamma, but not IL-4, was limited to intrapancreatic lymphocytes and was not detectable at extrapancreatic lymphoid sites. |
| 310 | 8617981 | Moreover, mAbs against IFN-gamma, but not against IL-4 or IL-2, prevent hyperglycemia and insulitis in MDSDM, suggesting that IFN-gamma regulates development of disease. |
| 311 | 8617981 | Cells in the pancreases of nondiabetic mice treated with anti-IFN-gamma mAb and STZ show enhanced expression of IL-4, but the prevention of disease is due to blockade of the IFN-gamma itself, and not due to secretion of IL-4, because systemic administration of IL-4 does not prevent MDSDM. |
| 312 | 8617981 | We have found that IL-2, IL-4, TNF-alpha, and IFN-gamma are expressed by the time the fourth dose of STZ is given. |
| 313 | 8617981 | However, expression of IFN-gamma, but not IL-4, was limited to intrapancreatic lymphocytes and was not detectable at extrapancreatic lymphoid sites. |
| 314 | 8617981 | Moreover, mAbs against IFN-gamma, but not against IL-4 or IL-2, prevent hyperglycemia and insulitis in MDSDM, suggesting that IFN-gamma regulates development of disease. |
| 315 | 8617981 | Cells in the pancreases of nondiabetic mice treated with anti-IFN-gamma mAb and STZ show enhanced expression of IL-4, but the prevention of disease is due to blockade of the IFN-gamma itself, and not due to secretion of IL-4, because systemic administration of IL-4 does not prevent MDSDM. |
| 316 | 8617981 | We have found that IL-2, IL-4, TNF-alpha, and IFN-gamma are expressed by the time the fourth dose of STZ is given. |
| 317 | 8617981 | However, expression of IFN-gamma, but not IL-4, was limited to intrapancreatic lymphocytes and was not detectable at extrapancreatic lymphoid sites. |
| 318 | 8617981 | Moreover, mAbs against IFN-gamma, but not against IL-4 or IL-2, prevent hyperglycemia and insulitis in MDSDM, suggesting that IFN-gamma regulates development of disease. |
| 319 | 8617981 | Cells in the pancreases of nondiabetic mice treated with anti-IFN-gamma mAb and STZ show enhanced expression of IL-4, but the prevention of disease is due to blockade of the IFN-gamma itself, and not due to secretion of IL-4, because systemic administration of IL-4 does not prevent MDSDM. |
| 320 | 8617981 | We have found that IL-2, IL-4, TNF-alpha, and IFN-gamma are expressed by the time the fourth dose of STZ is given. |
| 321 | 8617981 | However, expression of IFN-gamma, but not IL-4, was limited to intrapancreatic lymphocytes and was not detectable at extrapancreatic lymphoid sites. |
| 322 | 8617981 | Moreover, mAbs against IFN-gamma, but not against IL-4 or IL-2, prevent hyperglycemia and insulitis in MDSDM, suggesting that IFN-gamma regulates development of disease. |
| 323 | 8617981 | Cells in the pancreases of nondiabetic mice treated with anti-IFN-gamma mAb and STZ show enhanced expression of IL-4, but the prevention of disease is due to blockade of the IFN-gamma itself, and not due to secretion of IL-4, because systemic administration of IL-4 does not prevent MDSDM. |
| 324 | 8635648 | Tumor necrosis factor-alpha, IL-4, and IL-10 mRNA levels were not significantly different in islet leukocytes from the four groups of rats. |
| 325 | 8635648 | These findings suggest that production of T-helper 1 (Th1)-type cytokines, IFN-gamma and IL-2, by islet-infiltrating cells in BB rats is associated with beta-cell destruction and IDDM development. |
| 326 | 8635658 | Although it might have been predicted that the absence of IFN-gamma in these mice would lead to an increase in expression of Th2 T-helper cell-related cytokines, we found instead a profound decrease in the expression of two of the characteristic Th2 cytokines, interleukin (IL)-4 and IL-10. |
| 327 | 8650265 | IRS-signalling proteins are engaged and phosphorylated on tyrosine residues by the receptors for insulin and IGF-1, and various classes of cytokine receptors, including IL-4, IL-9, and IL-13; IFN alpha/beta and IFN gamma; and growth hormone and LIF. |
| 328 | 8660843 | Prostaglandin E2 inhibits the nuclear transcription of the human interleukin 2, but not the Il-4, gene in human T cells by targeting transcription factors AP-1 and NF-AT. |
| 329 | 8660843 | Using DNA transfection and electrophoretic mobility shift assays (EMSA), we have examined the mechanisms for the transcriptional regulation of human IL-2 and IL-4 genes by PGE2. |
| 330 | 8660843 | Stimulation of Jurkat cells with ionomycin and PMA in the presence of PGE2 inhibited the IL-2- but not the IL-4-promoter activity. |
| 331 | 8660843 | In EMSAs, nuclear extracts from primary human T cells stimulated with ionomycin and phorbol esters in the presence of PGE2 demonstrated decreased binding at the AP-1 and NF-AT sites of the human IL-2 promoter; binding to the OCT-1 and NF-kappa B sites was not affected. |
| 332 | 8660843 | Prostaglandin E2 inhibits the nuclear transcription of the human interleukin 2, but not the Il-4, gene in human T cells by targeting transcription factors AP-1 and NF-AT. |
| 333 | 8660843 | Using DNA transfection and electrophoretic mobility shift assays (EMSA), we have examined the mechanisms for the transcriptional regulation of human IL-2 and IL-4 genes by PGE2. |
| 334 | 8660843 | Stimulation of Jurkat cells with ionomycin and PMA in the presence of PGE2 inhibited the IL-2- but not the IL-4-promoter activity. |
| 335 | 8660843 | In EMSAs, nuclear extracts from primary human T cells stimulated with ionomycin and phorbol esters in the presence of PGE2 demonstrated decreased binding at the AP-1 and NF-AT sites of the human IL-2 promoter; binding to the OCT-1 and NF-kappa B sites was not affected. |
| 336 | 8660843 | Prostaglandin E2 inhibits the nuclear transcription of the human interleukin 2, but not the Il-4, gene in human T cells by targeting transcription factors AP-1 and NF-AT. |
| 337 | 8660843 | Using DNA transfection and electrophoretic mobility shift assays (EMSA), we have examined the mechanisms for the transcriptional regulation of human IL-2 and IL-4 genes by PGE2. |
| 338 | 8660843 | Stimulation of Jurkat cells with ionomycin and PMA in the presence of PGE2 inhibited the IL-2- but not the IL-4-promoter activity. |
| 339 | 8660843 | In EMSAs, nuclear extracts from primary human T cells stimulated with ionomycin and phorbol esters in the presence of PGE2 demonstrated decreased binding at the AP-1 and NF-AT sites of the human IL-2 promoter; binding to the OCT-1 and NF-kappa B sites was not affected. |
| 340 | 8664448 | During the early phase of insulitis from 6 to 12 weeks of age, mainly the monokines IL-1 alpha, IL-6, and TNF were detected. |
| 341 | 8664448 | After stimulation, also IFN-gamma and low numbers of IL-10 and GM-CSF producing cells could be observed, but no IL-2 or IL-4 was seen. |
| 342 | 8664448 | During a later phase, between 4 and 6 months, there is a characteristic TH1 cytokine profile with production of IL-2 and IFN-gamma occurring after stimulation, as well as lymphocytes producing TNF, supposedly TNF-beta. |
| 343 | 8664448 | During this period IL-10 was very rarely observed, and no IL-4 production could be found throughout the study. |
| 344 | 8664448 | During the early phase of insulitis from 6 to 12 weeks of age, mainly the monokines IL-1 alpha, IL-6, and TNF were detected. |
| 345 | 8664448 | After stimulation, also IFN-gamma and low numbers of IL-10 and GM-CSF producing cells could be observed, but no IL-2 or IL-4 was seen. |
| 346 | 8664448 | During a later phase, between 4 and 6 months, there is a characteristic TH1 cytokine profile with production of IL-2 and IFN-gamma occurring after stimulation, as well as lymphocytes producing TNF, supposedly TNF-beta. |
| 347 | 8664448 | During this period IL-10 was very rarely observed, and no IL-4 production could be found throughout the study. |
| 348 | 8671656 | Partially purified MLR-IA inhibits IL-2 production in a primary allo-MLR, and decreases IFN-gamma production during secondary allo-MLR and Con A activation, whereas it enhances IL-4 production in both primary and secondary Con A activation. |
| 349 | 8671656 | MLR-IA is not neutralized by combination of antibodies specific for transforming growth factor-beta, IL-10, tumor necrosis factor-alpha/beta or IFN-gamma, suggestive of a novel activity. |
| 350 | 8671656 | Our work suggests that a potentially novel immunoregulatory activity, capable of inhibiting T lymphocyte proliferation and IFN-gamma production, and stimulating IL-4 production, may regulate development of autoimmune diabetes in NOD mice. |
| 351 | 8671656 | Partially purified MLR-IA inhibits IL-2 production in a primary allo-MLR, and decreases IFN-gamma production during secondary allo-MLR and Con A activation, whereas it enhances IL-4 production in both primary and secondary Con A activation. |
| 352 | 8671656 | MLR-IA is not neutralized by combination of antibodies specific for transforming growth factor-beta, IL-10, tumor necrosis factor-alpha/beta or IFN-gamma, suggestive of a novel activity. |
| 353 | 8671656 | Our work suggests that a potentially novel immunoregulatory activity, capable of inhibiting T lymphocyte proliferation and IFN-gamma production, and stimulating IL-4 production, may regulate development of autoimmune diabetes in NOD mice. |
| 354 | 8674148 | TGF-beta 1, IL-10 and IL-4). |
| 355 | 8680958 | A potential immunoregulatory function has recently been attributed to the discrete subset of major histocompatibility complex (MHC) class I-restricted TCR-alpha beta mature thymocytes expressing an unusual V beta 8-biased T cell receptor repertoire. |
| 356 | 8680958 | This T cell subset which also selectively express the CD44 marker is the main IL-4 producer in the thymus. |
| 357 | 8680958 | Nonobese diabetic (NOD) mice were found to have a marked deficit in the number and functional capacity of CD44+ TCR-alpha beta+ thymocytes from as early as 3 weeks of age. |
| 358 | 8680958 | The deficiency in IL-4 production was completely corrected after incubation with interleukin-7 (IL-7), a selective growth factor for CD44+ TCR-alpha beta+ mature thymocytes. |
| 359 | 8680958 | A potential immunoregulatory function has recently been attributed to the discrete subset of major histocompatibility complex (MHC) class I-restricted TCR-alpha beta mature thymocytes expressing an unusual V beta 8-biased T cell receptor repertoire. |
| 360 | 8680958 | This T cell subset which also selectively express the CD44 marker is the main IL-4 producer in the thymus. |
| 361 | 8680958 | Nonobese diabetic (NOD) mice were found to have a marked deficit in the number and functional capacity of CD44+ TCR-alpha beta+ thymocytes from as early as 3 weeks of age. |
| 362 | 8680958 | The deficiency in IL-4 production was completely corrected after incubation with interleukin-7 (IL-7), a selective growth factor for CD44+ TCR-alpha beta+ mature thymocytes. |
| 363 | 8690153 | A significantly higher ratio of anti-CD3-induced interferon-gamma/interleukin-4 was found in diabetic NOD mice (P < 0.0001) but not in age-matched nondiabetic NOD mice. |
| 364 | 8706342 | Glutamic acid decarboxylase (GAD) could be a key antigen involved in this disease, and GAD65 peptide 524-543 has been implicated in early T cell response in young NOD mice. |
| 365 | 8706342 | After peptide challenge of splenocytes in vitro, protection against CY-accelerated diabetes was associated with higher peptide-specific production of T helper type 2 (Th2)-associated interleukins 4 and 10, whereas Th1-associated interferon-gamma and IL-2 were proportionally less represented. |
| 366 | 8706342 | It is concluded that immunization of NOD mice with GAD65 peptide 524-543 can counteract CY-accelerated diabetes, possibly through active cellular suppression linked to a shift of Th1/Th2 balance toward the production of Th2 cytokines such as IL-4 and IL-10. |
| 367 | 8720604 | To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-gamma), T helper 2 (interleukin-4 and interleukin-10) lymphocytes and macrophages (tumour necrosis factor-alpha, interleukin-1 alpha and interleukin-1 beta) in patients before and after the onset of IDDM. |
| 368 | 8720604 | Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-gamma, tumour necrosis factor-alpha and interleukin-1 alpha than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p < 0.05 for all). |
| 369 | 8720604 | Compared with control subjects, patients with long-standing IDDM and those with NIDDM had higher interleukin-2 and tumour necrosis factor-alpha levels (p < 0.01 for all). |
| 370 | 8720604 | Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 beta was not detectable in the serum of any control or test subject. |
| 371 | 8720604 | To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-gamma), T helper 2 (interleukin-4 and interleukin-10) lymphocytes and macrophages (tumour necrosis factor-alpha, interleukin-1 alpha and interleukin-1 beta) in patients before and after the onset of IDDM. |
| 372 | 8720604 | Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-gamma, tumour necrosis factor-alpha and interleukin-1 alpha than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p < 0.05 for all). |
| 373 | 8720604 | Compared with control subjects, patients with long-standing IDDM and those with NIDDM had higher interleukin-2 and tumour necrosis factor-alpha levels (p < 0.01 for all). |
| 374 | 8720604 | Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 beta was not detectable in the serum of any control or test subject. |
| 375 | 8724841 | Th1 cells produce IFN-gamma, which is the most powerful inducer of inducible NO synthase (iNOS). |
| 376 | 8724841 | In contrast, interleukin 4 is produced by Th2 cells and inhibits the induction of iNOS at the level of transcription. |
| 377 | 8757636 | However, reverse-transcription PCR and ELISA measurements of cytokine mRNA and protein levels showed that the GAD65-reactive T cells from both line 5 and line 12 mice produced higher levels of IL-4 and lower levels of IFN-gamma than similar T cells from standard NOD/Lt mice. |
| 378 | 8760354 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease in which cytokines are thought to play an important role in beta-cell destruction and immune regulation. |
| 379 | 8760354 | A major target of beta-cell autoimmunity in IDDM is the enzyme glutamate decarboxylase (GAD). |
| 380 | 8760354 | Accordingly we cultured rat islets in the presence and absence of cytokines, and measured synthesis of both isoforms of GAD, GAD65 and GAD67, by [35S]methionine incorporation and immunoprecipitation with a rabbit antiserum that recognizes both GAD65 and GAD67. |
| 381 | 8760354 | Incubation of islets with interleukin (IL)-1 beta (1 ng/ml, 24 h), tumour necrosis factor alpha (TNF-alpha; 200 units/ml, 24 h) or interferon gamma (IFN-gamma; 500 units/ml, 72 h) significantly decreased the synthesis of both GAD65 and GAD67, but reduced neither total protein synthesis nor insulin accumulation in the medium or content. |
| 382 | 8760354 | Incubation of islets for 24 h in IFN-alpha (1000 units/ml), TNF-beta (50 ng/ml), IL 2 (1000 units/ml), IL-4 (100 ng/ml), IL-6 (10 ng/ml), IL-10 (20 ng/ml), IL-12 (10 ng/ml) or transforming growth factor beta 2 (TGF-beta 2; 5 ng/ml) did not significantly alter GAD65 or GAD67 synthesis. |
| 383 | 8760354 | Inhibition of GAD65 and GAD67 protein synthesis by IL-1 beta, TNF-alpha or IFN-gamma was reversed by co-incubation with the nitric oxide synthase inhibitor, NG-monomethyl arginine (NMMA). |
| 384 | 8760354 | Expression of both GAD65 and GAD67 mRNA, measured by RNase protection assay, was also decreased by IL-1 beta and completely restored to baseline levels by NMMA. |
| 385 | 8760354 | Thus the synthesis of both isoforms of islet GAD is selectively decreased in the presence of IL-1 beta, TNF-alpha or IFN-gamma by a NO-mediated mechanism, probably at the level of cytokine gene transcription. |
| 386 | 8760354 | As GAD autoimmunity has been previously shown to have a pathogenic role in an animal model of IDDM, its inhibition by cytokines might limit the immune response, thereby regulating the rate of beta-cell destruction in IDDM. |
| 387 | 8777718 | Rapid IDDM was associated with increased numbers of anti-self CTL and a predominance of IFN gamma produced by islet-infiltrating lymphocytes, whereas single transgenic RIP-NP littermates with slow-onset IDDM displayed less anti-self CTL and more IL-4- and IL-10-producing T lymphocytes in pancreatic infiltrates. |
| 388 | 8808683 | Functional analyses of T cells isolated from CD28-deficient mice demonstrated that the GAD-specific T cells produced enhanced Th1-type cytokines (IL-2 and IFN gamma) and diminished Th2-type cytokine, IL-4. |
| 389 | 8816966 | Th1 cytokines are thought to play a key role in islet inflammation and destruction in insulin-dependent diabetes mellitus (IDDM). |
| 390 | 8816966 | In contrast, expression of message for IL-2 and IL-4 is minimal to undetectable in DP-BB and RT6-depleted DR-BB animals at any age. |
| 391 | 8816966 | Incubation of 10 wk old DP islets for 48 h in the presence of anti-CD3 antibody, followed by an incubation with rIL-2 for an additional 5-7 days, results in an expansion of T lymphocytes, and these cells express high levels of IFN-gamma and IL-10 mRNA. |
| 392 | 8816966 | Our results suggest that autoimmunity in DP-BB and DR-BB rats is mediated by Th1 lymphocytes and that IFN-gamma and IL-12 are likely to play a key role in islet and thyroid inflammation and destruction in IDDM. |
| 393 | 8816968 | Insulin-dependent diabetes mellitus (IDDM) in the non-obese diabetic (NOD) mouse results from effector T cell-mediated autoimmune processes directed against pancreatic beta cells. |
| 394 | 8816968 | The clone was found to produce substantial amounts of transforming growth factor beta (TGF-beta), IL-10, and IFN-gamma, but not IL-2 or IL-4, indicating that this T cell clone is not a member of either the classic Th1 or Th2 cell type. |
| 395 | 8816968 | On the basis of these observations, we suggest that a new type of CD4+ suppressor T cell, NY4.2, by secreting TGF-beta, can prevent effector T cell-mediated beta cell destruction. |
| 396 | 8816970 | Interventional approaches that have been successful in delaying insulin-dependent diabetes mellitus (IDDM) using antigen-based immunotherapies include parenteral immunization. |
| 397 | 8816970 | We have previously shown that immunization with insulin and insulin B chain but not A chain in incomplete Freund's adjuvant (IFA) prevented diabetes by reducing IFN-gamma mRNA in the insulitis lesions. |
| 398 | 8816970 | When Diphtheria-Tetanus toxoid-Acellular Pertussis (DTP) vaccine was used as the adjuvant vehicle, DTP itself induced significant protection (P < 0.003) which was associated with a Th2-like cytokine producing insulitis profile, IL-4 driven IgG1 antibody responses to insulin, GAD in the periphery and an augmentation of the autoimmune response to GAD. |
| 399 | 8816971 | Analysis of in vitro production of IFN gamma, IL-2 and IL-4 demonstrated a TH1 and TH0 like functional subset of the individual clones. |
| 400 | 8823297 | Here we report that oral treatment with insulin prevents virus-induced insulin-dependent diabetes mellitus (IDDM) in a transgenic (tg) mouse model. |
| 401 | 8823297 | Oral treatment with 1 mg of insulin twice per week for 2 mo starting either 1 wk before or 10 d after initiating LCMV infection prevents IDDM in > 50% of the tg mice (observation time 8 mo). |
| 402 | 8823297 | Thus, insulin therapy is effective in preventing progression to overt IDDM in prediabetic tg mice with ongoing islet infiltration. |
| 403 | 8823297 | However, less beta cells are destroyed in insulin-treated mice, upregulation of MHC class I and II molecules does not occur, and antiviral (self) cytotoxic T lymphocytes are not found in the islets, events present in tg mice developing IDDM. |
| 404 | 8823297 | The majority of lymphocytes in the islets of insulin-treated tg mice without IDDM produces IL-4, IL-10, and TGF-beta. |
| 405 | 8826970 | Both CD4+ and CD8+ T-cells in syngeneic islet grafts in NOD mice produce interferon-gamma during beta-cell destruction. |
| 406 | 8826970 | Islet grafts from CFA-injected mice contained fewer CD4+ and CD8+ cells and more B cells; also fewer interferon gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-alpha)-positive cells and more IL-4 and IL-10 positive cells. |
| 407 | 8826970 | By performing two-color immunostaining of cell surface antigens and intracellular IFN-gamma, we found that IFN-gamma positive cells in islet grafts from CFA- and PBS-injected mice were approximately equally divided between CD4+ and CD8+ T-cell subsets. |
| 408 | 8826970 | Also, the frequencies of both CD4+ IFN-gamma + and CD8+ IFN-gamma + cells were decreased in islet grafts from CFA-injected mice. |
| 409 | 8826970 | These findings suggest that destruction of beta-cells in syngeneic islets transplanted into NOD mice is promoted by cells producing Th1-type cytokines (IFN-gamma, IL-2, and TNF-alpha) and prevented by cells producing TH2-type cytokines (IL-4 and IL-10). |
| 410 | 8826970 | Furthermore, both CD4+ and CD8+ IFN-gamma-producing T-cells in the islet grafts appear to be involved in beta-cell destruction and diabetes recurrence. |
| 411 | 8826970 | Both CD4+ and CD8+ T-cells in syngeneic islet grafts in NOD mice produce interferon-gamma during beta-cell destruction. |
| 412 | 8826970 | Islet grafts from CFA-injected mice contained fewer CD4+ and CD8+ cells and more B cells; also fewer interferon gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-alpha)-positive cells and more IL-4 and IL-10 positive cells. |
| 413 | 8826970 | By performing two-color immunostaining of cell surface antigens and intracellular IFN-gamma, we found that IFN-gamma positive cells in islet grafts from CFA- and PBS-injected mice were approximately equally divided between CD4+ and CD8+ T-cell subsets. |
| 414 | 8826970 | Also, the frequencies of both CD4+ IFN-gamma + and CD8+ IFN-gamma + cells were decreased in islet grafts from CFA-injected mice. |
| 415 | 8826970 | These findings suggest that destruction of beta-cells in syngeneic islets transplanted into NOD mice is promoted by cells producing Th1-type cytokines (IFN-gamma, IL-2, and TNF-alpha) and prevented by cells producing TH2-type cytokines (IL-4 and IL-10). |
| 416 | 8826970 | Furthermore, both CD4+ and CD8+ IFN-gamma-producing T-cells in the islet grafts appear to be involved in beta-cell destruction and diabetes recurrence. |
| 417 | 8830831 | Primary nonfunction of islet grafts in autoimmune diabetic nonobese diabetic mice is prevented by treatment with interleukin-4 and interleukin-10. |
| 418 | 8830831 | Treatment of the recipients with the Th2-associated cytokine interleukin (IL)-4 alone did not prevent primary nonfunction, whereas treatment of the recipients with a combination of IL-4 and IL-10 restored immediate function of the grafts. |
| 419 | 8830831 | Histological analysis of the grafts revealed less severely infiltrated islets, with well preserved islet architecture, in only normoglycemic animals treated with IL-4 or with IL-4 and IL-10. |
| 420 | 8830831 | Staining for lymphocytes, macrophages, and tumor necrosis factor (TNF)-alpha did not show differences between the groups, but IFN-gamma was markedly less expressed in IL-4- and IL-10-treated grafts. |
| 421 | 8830831 | Concomitantly, analysis of animals treated for 8 days after injection of cyclophosphamide, with IL-4 and IL-10, revealed a reduction of IL-12 mRNA in the pancreas. |
| 422 | 8830831 | We conclude from these data that primary nonfunction of islet grafts is prevented by treatment of the recipients with a combination of IL-4 and IL-10, via downregulation of Th1 cytokines. |
| 423 | 8830831 | Primary nonfunction of islet grafts in autoimmune diabetic nonobese diabetic mice is prevented by treatment with interleukin-4 and interleukin-10. |
| 424 | 8830831 | Treatment of the recipients with the Th2-associated cytokine interleukin (IL)-4 alone did not prevent primary nonfunction, whereas treatment of the recipients with a combination of IL-4 and IL-10 restored immediate function of the grafts. |
| 425 | 8830831 | Histological analysis of the grafts revealed less severely infiltrated islets, with well preserved islet architecture, in only normoglycemic animals treated with IL-4 or with IL-4 and IL-10. |
| 426 | 8830831 | Staining for lymphocytes, macrophages, and tumor necrosis factor (TNF)-alpha did not show differences between the groups, but IFN-gamma was markedly less expressed in IL-4- and IL-10-treated grafts. |
| 427 | 8830831 | Concomitantly, analysis of animals treated for 8 days after injection of cyclophosphamide, with IL-4 and IL-10, revealed a reduction of IL-12 mRNA in the pancreas. |
| 428 | 8830831 | We conclude from these data that primary nonfunction of islet grafts is prevented by treatment of the recipients with a combination of IL-4 and IL-10, via downregulation of Th1 cytokines. |
| 429 | 8830831 | Primary nonfunction of islet grafts in autoimmune diabetic nonobese diabetic mice is prevented by treatment with interleukin-4 and interleukin-10. |
| 430 | 8830831 | Treatment of the recipients with the Th2-associated cytokine interleukin (IL)-4 alone did not prevent primary nonfunction, whereas treatment of the recipients with a combination of IL-4 and IL-10 restored immediate function of the grafts. |
| 431 | 8830831 | Histological analysis of the grafts revealed less severely infiltrated islets, with well preserved islet architecture, in only normoglycemic animals treated with IL-4 or with IL-4 and IL-10. |
| 432 | 8830831 | Staining for lymphocytes, macrophages, and tumor necrosis factor (TNF)-alpha did not show differences between the groups, but IFN-gamma was markedly less expressed in IL-4- and IL-10-treated grafts. |
| 433 | 8830831 | Concomitantly, analysis of animals treated for 8 days after injection of cyclophosphamide, with IL-4 and IL-10, revealed a reduction of IL-12 mRNA in the pancreas. |
| 434 | 8830831 | We conclude from these data that primary nonfunction of islet grafts is prevented by treatment of the recipients with a combination of IL-4 and IL-10, via downregulation of Th1 cytokines. |
| 435 | 8830831 | Primary nonfunction of islet grafts in autoimmune diabetic nonobese diabetic mice is prevented by treatment with interleukin-4 and interleukin-10. |
| 436 | 8830831 | Treatment of the recipients with the Th2-associated cytokine interleukin (IL)-4 alone did not prevent primary nonfunction, whereas treatment of the recipients with a combination of IL-4 and IL-10 restored immediate function of the grafts. |
| 437 | 8830831 | Histological analysis of the grafts revealed less severely infiltrated islets, with well preserved islet architecture, in only normoglycemic animals treated with IL-4 or with IL-4 and IL-10. |
| 438 | 8830831 | Staining for lymphocytes, macrophages, and tumor necrosis factor (TNF)-alpha did not show differences between the groups, but IFN-gamma was markedly less expressed in IL-4- and IL-10-treated grafts. |
| 439 | 8830831 | Concomitantly, analysis of animals treated for 8 days after injection of cyclophosphamide, with IL-4 and IL-10, revealed a reduction of IL-12 mRNA in the pancreas. |
| 440 | 8830831 | We conclude from these data that primary nonfunction of islet grafts is prevented by treatment of the recipients with a combination of IL-4 and IL-10, via downregulation of Th1 cytokines. |
| 441 | 8830831 | Primary nonfunction of islet grafts in autoimmune diabetic nonobese diabetic mice is prevented by treatment with interleukin-4 and interleukin-10. |
| 442 | 8830831 | Treatment of the recipients with the Th2-associated cytokine interleukin (IL)-4 alone did not prevent primary nonfunction, whereas treatment of the recipients with a combination of IL-4 and IL-10 restored immediate function of the grafts. |
| 443 | 8830831 | Histological analysis of the grafts revealed less severely infiltrated islets, with well preserved islet architecture, in only normoglycemic animals treated with IL-4 or with IL-4 and IL-10. |
| 444 | 8830831 | Staining for lymphocytes, macrophages, and tumor necrosis factor (TNF)-alpha did not show differences between the groups, but IFN-gamma was markedly less expressed in IL-4- and IL-10-treated grafts. |
| 445 | 8830831 | Concomitantly, analysis of animals treated for 8 days after injection of cyclophosphamide, with IL-4 and IL-10, revealed a reduction of IL-12 mRNA in the pancreas. |
| 446 | 8830831 | We conclude from these data that primary nonfunction of islet grafts is prevented by treatment of the recipients with a combination of IL-4 and IL-10, via downregulation of Th1 cytokines. |
| 447 | 8830831 | Primary nonfunction of islet grafts in autoimmune diabetic nonobese diabetic mice is prevented by treatment with interleukin-4 and interleukin-10. |
| 448 | 8830831 | Treatment of the recipients with the Th2-associated cytokine interleukin (IL)-4 alone did not prevent primary nonfunction, whereas treatment of the recipients with a combination of IL-4 and IL-10 restored immediate function of the grafts. |
| 449 | 8830831 | Histological analysis of the grafts revealed less severely infiltrated islets, with well preserved islet architecture, in only normoglycemic animals treated with IL-4 or with IL-4 and IL-10. |
| 450 | 8830831 | Staining for lymphocytes, macrophages, and tumor necrosis factor (TNF)-alpha did not show differences between the groups, but IFN-gamma was markedly less expressed in IL-4- and IL-10-treated grafts. |
| 451 | 8830831 | Concomitantly, analysis of animals treated for 8 days after injection of cyclophosphamide, with IL-4 and IL-10, revealed a reduction of IL-12 mRNA in the pancreas. |
| 452 | 8830831 | We conclude from these data that primary nonfunction of islet grafts is prevented by treatment of the recipients with a combination of IL-4 and IL-10, via downregulation of Th1 cytokines. |
| 453 | 8871765 | With a semi-quantitative reverse transcriptase-PCR assay, we examined whether the disease process was reflected in the profiles of TH1 (IL-2, IFN-gamma and IL-12) and TH2 (IL-4, IL-6 and IL-10) cytokine mRNAs expressed in pancreata of NOD mice. |
| 454 | 8906850 | Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus. |
| 455 | 8906850 | IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). |
| 456 | 8906850 | To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. |
| 457 | 8906850 | IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). |
| 458 | 8906850 | Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. |
| 459 | 8906850 | In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. |
| 460 | 8906850 | Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress. |
| 461 | 8906850 | Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus. |
| 462 | 8906850 | IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). |
| 463 | 8906850 | To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. |
| 464 | 8906850 | IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). |
| 465 | 8906850 | Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. |
| 466 | 8906850 | In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. |
| 467 | 8906850 | Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress. |
| 468 | 8906850 | Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus. |
| 469 | 8906850 | IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). |
| 470 | 8906850 | To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. |
| 471 | 8906850 | IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). |
| 472 | 8906850 | Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. |
| 473 | 8906850 | In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. |
| 474 | 8906850 | Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress. |
| 475 | 8906850 | Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus. |
| 476 | 8906850 | IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). |
| 477 | 8906850 | To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. |
| 478 | 8906850 | IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). |
| 479 | 8906850 | Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. |
| 480 | 8906850 | In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. |
| 481 | 8906850 | Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress. |
| 482 | 8906850 | Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus. |
| 483 | 8906850 | IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). |
| 484 | 8906850 | To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. |
| 485 | 8906850 | IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). |
| 486 | 8906850 | Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. |
| 487 | 8906850 | In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. |
| 488 | 8906850 | Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress. |
| 489 | 8906850 | Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus. |
| 490 | 8906850 | IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). |
| 491 | 8906850 | To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. |
| 492 | 8906850 | IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). |
| 493 | 8906850 | Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. |
| 494 | 8906850 | In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. |
| 495 | 8906850 | Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress. |
| 496 | 8943570 | IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse. |
| 497 | 8943570 | We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49. |
| 498 | 8943570 | In the present experiments, the addition of exogenous IL-7 completely restored IL-4 production by anti-TCR alpha beta-stimulated mature (HSA-CD8-) thymocytes in NOD mice. |
| 499 | 8943570 | A short 2 h preincubation with IL-7 was sufficient to restore both the expression of IL-4 mRNA and IL-4 production capacity. |
| 500 | 8943570 | This was related to a direct effect on NK1+ thymocytes since: (i) the effect of IL-7 was restricted to the non-mainstream MEL-14- 3G11- TCR alpha beta + subset which mostly concentrates the IL-4-producing capacity and (ii) IL-7 did not restore IL-4 production in class I-deficient mice which lack the NK1+ T cell subset. |
| 501 | 8943570 | These results were extended in vivo by showing that the IL-7 treatment significantly increased the anti-CD3 triggered IL-4 production by NK1+ T spleen cells. |
| 502 | 8943570 | IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse. |
| 503 | 8943570 | We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49. |
| 504 | 8943570 | In the present experiments, the addition of exogenous IL-7 completely restored IL-4 production by anti-TCR alpha beta-stimulated mature (HSA-CD8-) thymocytes in NOD mice. |
| 505 | 8943570 | A short 2 h preincubation with IL-7 was sufficient to restore both the expression of IL-4 mRNA and IL-4 production capacity. |
| 506 | 8943570 | This was related to a direct effect on NK1+ thymocytes since: (i) the effect of IL-7 was restricted to the non-mainstream MEL-14- 3G11- TCR alpha beta + subset which mostly concentrates the IL-4-producing capacity and (ii) IL-7 did not restore IL-4 production in class I-deficient mice which lack the NK1+ T cell subset. |
| 507 | 8943570 | These results were extended in vivo by showing that the IL-7 treatment significantly increased the anti-CD3 triggered IL-4 production by NK1+ T spleen cells. |
| 508 | 8943570 | IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse. |
| 509 | 8943570 | We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49. |
| 510 | 8943570 | In the present experiments, the addition of exogenous IL-7 completely restored IL-4 production by anti-TCR alpha beta-stimulated mature (HSA-CD8-) thymocytes in NOD mice. |
| 511 | 8943570 | A short 2 h preincubation with IL-7 was sufficient to restore both the expression of IL-4 mRNA and IL-4 production capacity. |
| 512 | 8943570 | This was related to a direct effect on NK1+ thymocytes since: (i) the effect of IL-7 was restricted to the non-mainstream MEL-14- 3G11- TCR alpha beta + subset which mostly concentrates the IL-4-producing capacity and (ii) IL-7 did not restore IL-4 production in class I-deficient mice which lack the NK1+ T cell subset. |
| 513 | 8943570 | These results were extended in vivo by showing that the IL-7 treatment significantly increased the anti-CD3 triggered IL-4 production by NK1+ T spleen cells. |
| 514 | 8943570 | IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse. |
| 515 | 8943570 | We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49. |
| 516 | 8943570 | In the present experiments, the addition of exogenous IL-7 completely restored IL-4 production by anti-TCR alpha beta-stimulated mature (HSA-CD8-) thymocytes in NOD mice. |
| 517 | 8943570 | A short 2 h preincubation with IL-7 was sufficient to restore both the expression of IL-4 mRNA and IL-4 production capacity. |
| 518 | 8943570 | This was related to a direct effect on NK1+ thymocytes since: (i) the effect of IL-7 was restricted to the non-mainstream MEL-14- 3G11- TCR alpha beta + subset which mostly concentrates the IL-4-producing capacity and (ii) IL-7 did not restore IL-4 production in class I-deficient mice which lack the NK1+ T cell subset. |
| 519 | 8943570 | These results were extended in vivo by showing that the IL-7 treatment significantly increased the anti-CD3 triggered IL-4 production by NK1+ T spleen cells. |
| 520 | 8943570 | IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse. |
| 521 | 8943570 | We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49. |
| 522 | 8943570 | In the present experiments, the addition of exogenous IL-7 completely restored IL-4 production by anti-TCR alpha beta-stimulated mature (HSA-CD8-) thymocytes in NOD mice. |
| 523 | 8943570 | A short 2 h preincubation with IL-7 was sufficient to restore both the expression of IL-4 mRNA and IL-4 production capacity. |
| 524 | 8943570 | This was related to a direct effect on NK1+ thymocytes since: (i) the effect of IL-7 was restricted to the non-mainstream MEL-14- 3G11- TCR alpha beta + subset which mostly concentrates the IL-4-producing capacity and (ii) IL-7 did not restore IL-4 production in class I-deficient mice which lack the NK1+ T cell subset. |
| 525 | 8943570 | These results were extended in vivo by showing that the IL-7 treatment significantly increased the anti-CD3 triggered IL-4 production by NK1+ T spleen cells. |
| 526 | 8961238 | These shared symptoms include elevated tumour necrosis factor-alpha, down-regulated interleukin-2 and interleukin-4 and depletion of lean body mass. |
| 527 | 8961238 | Furthermore, the following neuropeptides are dysregulated in both anorexia nervosa and cancer cachexia: vasoactive intestinal peptide, cholecystokinin, corticotropin-releasing factor, neuropeptide Y, peptide YY and beta-endorphin. |
| 528 | 8968689 | Dominant TCR alpha-chain clonotypes and interferon-gamma are expressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus. |
| 529 | 8968689 | In order to clarify the nature of T lymphocytes infiltrating the pancreatic islets of patients with insulin-dependent diabetes mellitus (IDDM), we analysed T cell receptor (TCR) gene transcripts expressed in pancreatic biopsy specimens of patients with recent-onset IDDM. |
| 530 | 8968689 | We also investigated the expression of cytokines (interferon-gamma: IFN-gamma; tumour necrosis factor-alpha: TNF-alpha; interleukin-4: IL-4; interleukin-6: IL-6) in the same specimens. |
| 531 | 8968689 | IFN-gamma mRNA was highly expressed in the pancreas of IDDM patients, while IL-4 mRNA was deficient. |
| 532 | 8968689 | A lower level of expression of IL-6 mRNA was detected in the IDDM pancreas than in the control tissue. |
| 533 | 8968689 | Dominant TCR alpha-chain clonotypes and interferon-gamma are expressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus. |
| 534 | 8968689 | In order to clarify the nature of T lymphocytes infiltrating the pancreatic islets of patients with insulin-dependent diabetes mellitus (IDDM), we analysed T cell receptor (TCR) gene transcripts expressed in pancreatic biopsy specimens of patients with recent-onset IDDM. |
| 535 | 8968689 | We also investigated the expression of cytokines (interferon-gamma: IFN-gamma; tumour necrosis factor-alpha: TNF-alpha; interleukin-4: IL-4; interleukin-6: IL-6) in the same specimens. |
| 536 | 8968689 | IFN-gamma mRNA was highly expressed in the pancreas of IDDM patients, while IL-4 mRNA was deficient. |
| 537 | 8968689 | A lower level of expression of IL-6 mRNA was detected in the IDDM pancreas than in the control tissue. |
| 538 | 8976172 | Aerosol insulin induces regulatory CD8 gamma delta T cells that prevent murine insulin-dependent diabetes. |
| 539 | 8976172 | Insulin is an autoantigen in humans and nonobese diabetic (NOD) mice with insulin-dependent diabetes mellitus (IDDM). |
| 540 | 8976172 | Insulin-treated mice had increased circulating antibodies to insulin, absent splenocyte proliferation to the major epitope, insulin B chain amino acids 9-23, which was associated with increased IL-4 and particularly IL-10 secretion, and reduced proliferation to glutamic acid decarboxylase, another islet autoantigen. |
| 541 | 8976172 | The ability of splenocytes from insulin-treated mice to suppress the adoptive transfer of diabetes to nondiabetic mice by T cells of diabetic mice was shown to be caused by small numbers of CD8 gamma delta T cells. |
| 542 | 8976172 | Induction of regulatory CD8 gamma delta T cells by aerosol insulin is a therapeutic strategy with implications for the prevention of human IDDM. |
| 543 | 9000700 | Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. |
| 544 | 9000700 | Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. |
| 545 | 9000700 | Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). |
| 546 | 9000700 | However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). |
| 547 | 9000700 | Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. |
| 548 | 9000700 | Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. |
| 549 | 9000700 | Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). |
| 550 | 9000700 | However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). |
| 551 | 9000700 | Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. |
| 552 | 9000700 | Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. |
| 553 | 9000700 | Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). |
| 554 | 9000700 | However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). |
| 555 | 9046967 | Low doses of oral antigen induce antigen-specific regulatory T-cells in the gut, which act by releasing inhibitory cytokines such as transforming growth factor-beta, interleukin-4, and interleukin-10 at the target organ. |
| 556 | 9046967 | A double-blind, placebo-controlled, phase III multi-center trial of oral myelin in 515 relapsing-remitting multiple sclerosis patients is in progress, as are phase II clinical trials investigating the oral administration of type II collagen in rheumatoid arthritis, S-antigen in uveitis, and insulin in type I diabetes. |
| 557 | 9058834 | The tolerogenic properties of 145 2C11 did not depend on its mitogenic capacity, since nonmitogenic F(ab')2 fragments also appeared potent at inducing durable remission in overtly diabetic NOD, although nonmitogenic CD3 F(ab')2 fragments could mediate T cell signaling, as evidenced by cytokine gene transcription (IL-2, IFN-gamma, IL-4, and IL-10) assessed by PCR on splenocytes from treated mice. |
| 558 | 9064326 | To test this hypothesis, we generated transgenic NOD mice that express interleukin (IL) 4 in their pancreatic beta cells under the control of the human insulin promoter. |
| 559 | 9123210 | IL-2 and IL-4 double knock-out mice reject islet allografts: a role for novel T-cell growth factors? |
| 560 | 9127018 | Immunohistochemistry studies show that IL-10/Fc treatment inhibits expression of TNF-alpha, proinflammatory cytokine, as well as Th1-type cytokines, IL-2 and IFN-gamma, but promotes expression of IL-4 and IL-10, Th2-type cytokines, by islet-infiltrating leukocytes. |
| 561 | 9133541 | We now report that the effectiveness of p277 treatment is associated with the transient activation of anti-p277 splenic T-cells that produce the Th2 cytokines interleukin-4 (IL-4) and IL-10. |
| 562 | 9184917 | Production of both IFN-gamma and IL-5 by Onchocerca volvulus S1 antigen-specific CD4+ T cells from putatively immune individuals. |
| 563 | 9184917 | These clones, which are the first generated against a recombinant fllarial antigen, produced both IFN-gamma and IL-5 as well as little IL-4, suggestive of a Th0-like phenotype. |
| 564 | 9184917 | Induction of both IFN-gamma and IL-5 by S1 suggests that it may trigger macrophage plus eosinophil dependent killing of L3 in vivo. |
| 565 | 9185876 | The cell recruitment phase, between 6 and 12 weeks of age, is predominated by production of the monokines IL-1alpha, IL-6, and TNF After stimulation IFN-gamma and occasional IL-10 and GM-CSF producing cells could also be observed. |
| 566 | 9185876 | During the effector phase, between 4 and 6 months, there is a characteristic Th1 cytokine profile with lymphocytes producing IL-2, IFN-gamma and TNF, supposedly TNF-beta. |
| 567 | 9185876 | No IL-4 production could be detected and IL-10 was very rarely found, indicating the absence of a Th2 response. |
| 568 | 9200487 | Measurement of the macrophage-derived cytokines IL-12, TNF-alpha, and IL-1beta revealed a selective increase of their expression, after KRV infection, in the splenic lymphocytes and the pancreatic islets. |
| 569 | 9200487 | Measurement of CD4+ T cell-derived cytokines revealed that IL-2 and IFN-gamma cytokine gene expression closely correlates with an elevation of IL-12, but IL-4 and IL-10 do not change. |
| 570 | 9207862 | At doses approximating those achieved in vivo (0.4 and 2 micrograms/ml), dapsone was found to inhibit murine splenocyte IL-2 and IL-4 secretion in response to concanavalin A. |
| 571 | 9218751 | Systemic production of interferon-gamma inducing factor (IGIF) versus local IFN-gamma expression involved in the development of Th1 insulitis in NOD mice. |
| 572 | 9218751 | We report that the onset of Th1 insulitis is preceded by a rise of interferon-gamma inducing factor (IGIF) mRNA expression in the spleen. |
| 573 | 9218751 | Interestingly, immunohistochemistry showed IL-4-positive cells evenly dispersed throughout the infiltrate, while IFN-gamma-positive cells were restricted to the vicinity of beta-cells. |
| 574 | 9218754 | BCG vaccination prevents insulin-dependent diabetes mellitus (IDDM) in NOD mice after disease acceleration with cyclophosphamide. |
| 575 | 9218754 | We have previously shown that immunotherapy with complete Freund's adjuvant (CFA) or BCG is highly effective in the prevention of spontaneous insulin-dependent diabetes mellitus (IDDM) and in circumventing the rejection of syngeneic islet grafts in diabetic NOD mice. |
| 576 | 9218754 | The comprehensive effect of BCG vaccination on cytokine production in Cy-treated mice was to increase IL-4 production and change the IL-4/IFN-gamma ratio in both serum and supernatant of spleen cell cultures. |
| 577 | 9218754 | We found that BCG-induced protection was associated with increased splenic CD4+CD45 RB(high) T cells. |
| 578 | 9221759 | Autoimmune diabetes is caused by the CD4(+), T helper 1 (Th1) cell-mediated apoptosis of insulin-producing beta cells. |
| 579 | 9221759 | Moreover, the Th2-mediated destruction of islet cells was mediated by local interleukin-10 (IL-10) production but not by IL-4. |
| 580 | 9237797 | When those cells were cultured and restimulated in vitro with the B-chain of insulin, we also observed a decrease in IFN-gamma expression and an increase in IL-4, TGF-beta and IL-10 expression. |
| 581 | 9267984 | Potentiation of the effect of oral insulin by the adjuvant was associated with upregulation of interleukin (IL)-4 Th2 cells in infiltrated islets and sustained local IL-2 gene expression. |
| 582 | 9267984 | RT PCR analyses of cytokine expression in the gut showed a clear deviation to Th2 type reactivity and downregulation of inducible nitric oxide (NO) synthase (iNOS) expression by the bacterial adjuvant but not by oral insulin alone. |
| 583 | 9298104 | Analysis of cytokine production revealed lower interferon-gamma production in the LC-treated group compared to the control group, while the interleukin (IL)-2 production was higher. |
| 584 | 9298104 | The levels of IL-4, IL-5, IL-6 and IL-10 in the LC-treated group were somewhat higher than in the control group. |
| 585 | 9336387 | Increasing evidence suggests that cytokines such as interleukin-1beta (IL-1), IL-4, and IL-8 may play an important role in the chronic inflammation and cellular growth observed in cardiovascular diseases. |
| 586 | 9336387 | Furthermore, earlier studies have shown that vascular smooth muscle cell (VSMC) growth factors such as angiotensin II and platelet-derived growth factor can increase LO activity and expression in VSMCs. |
| 587 | 9336387 | In the present study, we have examined whether vasoactive and inflammatory cytokines such as IL-1, IL-4, and IL-8 can modulate 12-LO activity and expression in porcine VSMCs and also whether they have growth-promoting effects in these cells. |
| 588 | 9336387 | Increasing evidence suggests that cytokines such as interleukin-1beta (IL-1), IL-4, and IL-8 may play an important role in the chronic inflammation and cellular growth observed in cardiovascular diseases. |
| 589 | 9336387 | Furthermore, earlier studies have shown that vascular smooth muscle cell (VSMC) growth factors such as angiotensin II and platelet-derived growth factor can increase LO activity and expression in VSMCs. |
| 590 | 9336387 | In the present study, we have examined whether vasoactive and inflammatory cytokines such as IL-1, IL-4, and IL-8 can modulate 12-LO activity and expression in porcine VSMCs and also whether they have growth-promoting effects in these cells. |
| 591 | 9366391 | IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. |
| 592 | 9366391 | Beginning at the time of insulitis, nonobese diabetic (NOD) mice demonstrate a thymocyte and peripheral T cell proliferative hyporesponsiveness induced by TCR cross-linking, which is associated with reduced IL-2 and IL-4 secretion. |
| 593 | 9366391 | We previously reported that NOD CD4+ T cell hyporesponsiveness is reversed completely in vitro by exogenous IL-4, and that administration of IL-4 to NOD mice prevents the onset of insulin-dependent diabetes mellitus (IDDM). |
| 594 | 9366391 | In the present study, we tested this possibility by analysis of the mechanisms of protection from IDDM afforded by IL-4 treatment in NOD mice. |
| 595 | 9366391 | We show that IL-4 protects NOD mice from insulitis and IDDM when administered i.p. three times a week for 10 wk beginning at 2 wk of age. |
| 596 | 9366391 | Thus, IL-4 treatment favors the expansion of regulatory CD4+ Th2 cells in vivo and prevents the onset of insulitis and IDDM mediated by autoreactive Th1 cells. |
| 597 | 9366391 | IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. |
| 598 | 9366391 | Beginning at the time of insulitis, nonobese diabetic (NOD) mice demonstrate a thymocyte and peripheral T cell proliferative hyporesponsiveness induced by TCR cross-linking, which is associated with reduced IL-2 and IL-4 secretion. |
| 599 | 9366391 | We previously reported that NOD CD4+ T cell hyporesponsiveness is reversed completely in vitro by exogenous IL-4, and that administration of IL-4 to NOD mice prevents the onset of insulin-dependent diabetes mellitus (IDDM). |
| 600 | 9366391 | In the present study, we tested this possibility by analysis of the mechanisms of protection from IDDM afforded by IL-4 treatment in NOD mice. |
| 601 | 9366391 | We show that IL-4 protects NOD mice from insulitis and IDDM when administered i.p. three times a week for 10 wk beginning at 2 wk of age. |
| 602 | 9366391 | Thus, IL-4 treatment favors the expansion of regulatory CD4+ Th2 cells in vivo and prevents the onset of insulitis and IDDM mediated by autoreactive Th1 cells. |
| 603 | 9366391 | IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. |
| 604 | 9366391 | Beginning at the time of insulitis, nonobese diabetic (NOD) mice demonstrate a thymocyte and peripheral T cell proliferative hyporesponsiveness induced by TCR cross-linking, which is associated with reduced IL-2 and IL-4 secretion. |
| 605 | 9366391 | We previously reported that NOD CD4+ T cell hyporesponsiveness is reversed completely in vitro by exogenous IL-4, and that administration of IL-4 to NOD mice prevents the onset of insulin-dependent diabetes mellitus (IDDM). |
| 606 | 9366391 | In the present study, we tested this possibility by analysis of the mechanisms of protection from IDDM afforded by IL-4 treatment in NOD mice. |
| 607 | 9366391 | We show that IL-4 protects NOD mice from insulitis and IDDM when administered i.p. three times a week for 10 wk beginning at 2 wk of age. |
| 608 | 9366391 | Thus, IL-4 treatment favors the expansion of regulatory CD4+ Th2 cells in vivo and prevents the onset of insulitis and IDDM mediated by autoreactive Th1 cells. |
| 609 | 9366391 | IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. |
| 610 | 9366391 | Beginning at the time of insulitis, nonobese diabetic (NOD) mice demonstrate a thymocyte and peripheral T cell proliferative hyporesponsiveness induced by TCR cross-linking, which is associated with reduced IL-2 and IL-4 secretion. |
| 611 | 9366391 | We previously reported that NOD CD4+ T cell hyporesponsiveness is reversed completely in vitro by exogenous IL-4, and that administration of IL-4 to NOD mice prevents the onset of insulin-dependent diabetes mellitus (IDDM). |
| 612 | 9366391 | In the present study, we tested this possibility by analysis of the mechanisms of protection from IDDM afforded by IL-4 treatment in NOD mice. |
| 613 | 9366391 | We show that IL-4 protects NOD mice from insulitis and IDDM when administered i.p. three times a week for 10 wk beginning at 2 wk of age. |
| 614 | 9366391 | Thus, IL-4 treatment favors the expansion of regulatory CD4+ Th2 cells in vivo and prevents the onset of insulitis and IDDM mediated by autoreactive Th1 cells. |
| 615 | 9366391 | IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. |
| 616 | 9366391 | Beginning at the time of insulitis, nonobese diabetic (NOD) mice demonstrate a thymocyte and peripheral T cell proliferative hyporesponsiveness induced by TCR cross-linking, which is associated with reduced IL-2 and IL-4 secretion. |
| 617 | 9366391 | We previously reported that NOD CD4+ T cell hyporesponsiveness is reversed completely in vitro by exogenous IL-4, and that administration of IL-4 to NOD mice prevents the onset of insulin-dependent diabetes mellitus (IDDM). |
| 618 | 9366391 | In the present study, we tested this possibility by analysis of the mechanisms of protection from IDDM afforded by IL-4 treatment in NOD mice. |
| 619 | 9366391 | We show that IL-4 protects NOD mice from insulitis and IDDM when administered i.p. three times a week for 10 wk beginning at 2 wk of age. |
| 620 | 9366391 | Thus, IL-4 treatment favors the expansion of regulatory CD4+ Th2 cells in vivo and prevents the onset of insulitis and IDDM mediated by autoreactive Th1 cells. |
| 621 | 9366391 | IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. |
| 622 | 9366391 | Beginning at the time of insulitis, nonobese diabetic (NOD) mice demonstrate a thymocyte and peripheral T cell proliferative hyporesponsiveness induced by TCR cross-linking, which is associated with reduced IL-2 and IL-4 secretion. |
| 623 | 9366391 | We previously reported that NOD CD4+ T cell hyporesponsiveness is reversed completely in vitro by exogenous IL-4, and that administration of IL-4 to NOD mice prevents the onset of insulin-dependent diabetes mellitus (IDDM). |
| 624 | 9366391 | In the present study, we tested this possibility by analysis of the mechanisms of protection from IDDM afforded by IL-4 treatment in NOD mice. |
| 625 | 9366391 | We show that IL-4 protects NOD mice from insulitis and IDDM when administered i.p. three times a week for 10 wk beginning at 2 wk of age. |
| 626 | 9366391 | Thus, IL-4 treatment favors the expansion of regulatory CD4+ Th2 cells in vivo and prevents the onset of insulitis and IDDM mediated by autoreactive Th1 cells. |
| 627 | 9379064 | CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice. |
| 628 | 9379064 | Here, we investigate the role of CD40 ligand (CD40L)-CD40 costimulation in the initiation and progression of this disease. |
| 629 | 9379064 | Cytokine analysis revealed a dramatic decrease in IFN-gamma and IL-2 release without a concomitant increase in IL-4 production by T cells from anti-CD40L-treated mice. |
| 630 | 9381527 | Interleukin-4 or interleukin-10 expressed from adenovirus-transduced syngeneic islet grafts fails to prevent beta cell destruction in diabetic NOD mice. |
| 631 | 9392483 | Quite unexpectedly, two GAD65-derived peptides near the COOH-terminus (p34 and p35) accelerated diabetes onset. |
| 632 | 9392483 | Protection mediated by intrathymic administration with either intact islet cells or GAD65 were correlated with an upregulation of mRNA for T-helper 2 (Th2)-associated cytokines (interleukin [IL]-4, IL-10), concomitant with downregulation of Th1-associated interferon (IFN) transcripts (all normalized to T-cell receptor Cbeta transcripts) in islet-infiltrating lymphocytes. |
| 633 | 9392483 | Protection mediated by the intrathymic administration of insulin B chain, however, correlated only with a modest upregulation of IL-4 and IL-10 transcript levels, and no diminution in IFN-gamma transcripts. |
| 634 | 9392483 | In contrast, the diabetes-accelerating GAD65 p34 and p35 peptides were not associated with an immune deviation, expressing levels of IFN-gamma characteristic of islet-infiltrating lymphocytes in vehicle-injected NOD controls. |
| 635 | 9392483 | Quite unexpectedly, two GAD65-derived peptides near the COOH-terminus (p34 and p35) accelerated diabetes onset. |
| 636 | 9392483 | Protection mediated by intrathymic administration with either intact islet cells or GAD65 were correlated with an upregulation of mRNA for T-helper 2 (Th2)-associated cytokines (interleukin [IL]-4, IL-10), concomitant with downregulation of Th1-associated interferon (IFN) transcripts (all normalized to T-cell receptor Cbeta transcripts) in islet-infiltrating lymphocytes. |
| 637 | 9392483 | Protection mediated by the intrathymic administration of insulin B chain, however, correlated only with a modest upregulation of IL-4 and IL-10 transcript levels, and no diminution in IFN-gamma transcripts. |
| 638 | 9392483 | In contrast, the diabetes-accelerating GAD65 p34 and p35 peptides were not associated with an immune deviation, expressing levels of IFN-gamma characteristic of islet-infiltrating lymphocytes in vehicle-injected NOD controls. |
| 639 | 9410902 | Neonatal activation of CD28 signaling overcomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism. |
| 640 | 9410902 | Previously, we showed that T cells from autoimmune nonobese diabetic (NOD) mice display proliferative hyporesponsiveness to TCR stimulation, which may be causal to the development of insulin-dependent diabetes mellitus (IDDM). |
| 641 | 9410902 | Whereas neonatal treatment of NOD mice with anti-CD28 beginning at 2 wk of age inhibits destructive insulitis and protects against IDDM by enhancement of IL-4 production by islet-infiltrating T cells, administration of anti-CD28 beginning at 5-6 wk of age does not prevent IDDM. |
| 642 | 9410902 | Thus, neonatal CD28 costimulation during 2-4 wk of age is required to prevent IDDM, and is mediated by the generation of a Th2 cell-enriched nondestructive environment in the pancreatic islets of treated NOD mice. |
| 643 | 9410902 | Our data support the hypothesis that a CD28 signal is requisite for activation of IL-4-producing cells and protection from IDDM. |
| 644 | 9410902 | Neonatal activation of CD28 signaling overcomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism. |
| 645 | 9410902 | Previously, we showed that T cells from autoimmune nonobese diabetic (NOD) mice display proliferative hyporesponsiveness to TCR stimulation, which may be causal to the development of insulin-dependent diabetes mellitus (IDDM). |
| 646 | 9410902 | Whereas neonatal treatment of NOD mice with anti-CD28 beginning at 2 wk of age inhibits destructive insulitis and protects against IDDM by enhancement of IL-4 production by islet-infiltrating T cells, administration of anti-CD28 beginning at 5-6 wk of age does not prevent IDDM. |
| 647 | 9410902 | Thus, neonatal CD28 costimulation during 2-4 wk of age is required to prevent IDDM, and is mediated by the generation of a Th2 cell-enriched nondestructive environment in the pancreatic islets of treated NOD mice. |
| 648 | 9410902 | Our data support the hypothesis that a CD28 signal is requisite for activation of IL-4-producing cells and protection from IDDM. |
| 649 | 9410902 | Neonatal activation of CD28 signaling overcomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism. |
| 650 | 9410902 | Previously, we showed that T cells from autoimmune nonobese diabetic (NOD) mice display proliferative hyporesponsiveness to TCR stimulation, which may be causal to the development of insulin-dependent diabetes mellitus (IDDM). |
| 651 | 9410902 | Whereas neonatal treatment of NOD mice with anti-CD28 beginning at 2 wk of age inhibits destructive insulitis and protects against IDDM by enhancement of IL-4 production by islet-infiltrating T cells, administration of anti-CD28 beginning at 5-6 wk of age does not prevent IDDM. |
| 652 | 9410902 | Thus, neonatal CD28 costimulation during 2-4 wk of age is required to prevent IDDM, and is mediated by the generation of a Th2 cell-enriched nondestructive environment in the pancreatic islets of treated NOD mice. |
| 653 | 9410902 | Our data support the hypothesis that a CD28 signal is requisite for activation of IL-4-producing cells and protection from IDDM. |
| 654 | 9416430 | The ability of splenocytes to proliferate, respond to, or secrete interleukin-2 and interleukin-4 was explored in young, pre-diabetic or old non-diabetic female NOD mice. |
| 655 | 9416430 | These results suggest that diabetes induction is preceded by V beta + subset-specific functional changes in the ability of various T cells to respond to or secrete interleukin-2 and interleukin-4, indicating a functional imbalance of the T-cell repertoire expanded by the autoimmune process. |
| 656 | 9416430 | The ability of splenocytes to proliferate, respond to, or secrete interleukin-2 and interleukin-4 was explored in young, pre-diabetic or old non-diabetic female NOD mice. |
| 657 | 9416430 | These results suggest that diabetes induction is preceded by V beta + subset-specific functional changes in the ability of various T cells to respond to or secrete interleukin-2 and interleukin-4, indicating a functional imbalance of the T-cell repertoire expanded by the autoimmune process. |
| 658 | 9419441 | We therefore tested the hypothesis that stimulation of a Th2 response by either IL-4 or CD28 costimulation may block progression to IDDM. |
| 659 | 9421372 | Protection against autoimmune diabetes with oral insulin is associated with the presence of IL-4 type 2 T-cells in the pancreas and pancreatic lymph nodes. |
| 660 | 9421372 | In the present study, immunohistochemical analysis of the pancreatic glands revealed that injection of T-cells from insulin-fed mice upregulated the number of interleukin (IL)-4-secreting cells within the islets. |
| 661 | 9421372 | Using two strains of NOD mice congenic at the Tbeta, or Thy1, locus, we observed a higher proportion of T-cells from insulin-fed mice in both the spleen (7.73 +/- 0.3 vs. 5.57 +/- 0.2%; P < 0.001) and the pancreatic lymph nodes (10.1 +/- 0.8 vs. 7.2 +/- 0.7%; P < 0.05) of cotransferred mice. |
| 662 | 9421372 | By reverse transcription-polymerase chain reaction (RT-PCR) analysis, mice reconstituted with T-cells from insulin-fed animals had detectable amounts of IL-4 mRNA, specifically in the pancreatic lymph nodes (8 of 9 experimental mice vs. 1 of 9 control mice) and the pancreas (3 of 3 experimental mice vs. 0 of 3 control mice). |
| 663 | 9421372 | Gamma-interferon mRNA was detectable in all cotransferred animals, but IL-10 mRNA and transforming growth factor beta mRNA were undetectable. |
| 664 | 9421372 | We concluded that oral administration of insulin can induce the presence of regulatory T-cells in the pancreas and the corresponding draining lymph nodes, initiate the secretion of IL-4 in this microenvironment sufficiently to suppress the activity of Th1 autoreactive T-cell clones, and ultimately provide protection against autoimmune diabetes. |
| 665 | 9421372 | Protection against autoimmune diabetes with oral insulin is associated with the presence of IL-4 type 2 T-cells in the pancreas and pancreatic lymph nodes. |
| 666 | 9421372 | In the present study, immunohistochemical analysis of the pancreatic glands revealed that injection of T-cells from insulin-fed mice upregulated the number of interleukin (IL)-4-secreting cells within the islets. |
| 667 | 9421372 | Using two strains of NOD mice congenic at the Tbeta, or Thy1, locus, we observed a higher proportion of T-cells from insulin-fed mice in both the spleen (7.73 +/- 0.3 vs. 5.57 +/- 0.2%; P < 0.001) and the pancreatic lymph nodes (10.1 +/- 0.8 vs. 7.2 +/- 0.7%; P < 0.05) of cotransferred mice. |
| 668 | 9421372 | By reverse transcription-polymerase chain reaction (RT-PCR) analysis, mice reconstituted with T-cells from insulin-fed animals had detectable amounts of IL-4 mRNA, specifically in the pancreatic lymph nodes (8 of 9 experimental mice vs. 1 of 9 control mice) and the pancreas (3 of 3 experimental mice vs. 0 of 3 control mice). |
| 669 | 9421372 | Gamma-interferon mRNA was detectable in all cotransferred animals, but IL-10 mRNA and transforming growth factor beta mRNA were undetectable. |
| 670 | 9421372 | We concluded that oral administration of insulin can induce the presence of regulatory T-cells in the pancreas and the corresponding draining lymph nodes, initiate the secretion of IL-4 in this microenvironment sufficiently to suppress the activity of Th1 autoreactive T-cell clones, and ultimately provide protection against autoimmune diabetes. |
| 671 | 9421372 | Protection against autoimmune diabetes with oral insulin is associated with the presence of IL-4 type 2 T-cells in the pancreas and pancreatic lymph nodes. |
| 672 | 9421372 | In the present study, immunohistochemical analysis of the pancreatic glands revealed that injection of T-cells from insulin-fed mice upregulated the number of interleukin (IL)-4-secreting cells within the islets. |
| 673 | 9421372 | Using two strains of NOD mice congenic at the Tbeta, or Thy1, locus, we observed a higher proportion of T-cells from insulin-fed mice in both the spleen (7.73 +/- 0.3 vs. 5.57 +/- 0.2%; P < 0.001) and the pancreatic lymph nodes (10.1 +/- 0.8 vs. 7.2 +/- 0.7%; P < 0.05) of cotransferred mice. |
| 674 | 9421372 | By reverse transcription-polymerase chain reaction (RT-PCR) analysis, mice reconstituted with T-cells from insulin-fed animals had detectable amounts of IL-4 mRNA, specifically in the pancreatic lymph nodes (8 of 9 experimental mice vs. 1 of 9 control mice) and the pancreas (3 of 3 experimental mice vs. 0 of 3 control mice). |
| 675 | 9421372 | Gamma-interferon mRNA was detectable in all cotransferred animals, but IL-10 mRNA and transforming growth factor beta mRNA were undetectable. |
| 676 | 9421372 | We concluded that oral administration of insulin can induce the presence of regulatory T-cells in the pancreas and the corresponding draining lymph nodes, initiate the secretion of IL-4 in this microenvironment sufficiently to suppress the activity of Th1 autoreactive T-cell clones, and ultimately provide protection against autoimmune diabetes. |
| 677 | 9421372 | Protection against autoimmune diabetes with oral insulin is associated with the presence of IL-4 type 2 T-cells in the pancreas and pancreatic lymph nodes. |
| 678 | 9421372 | In the present study, immunohistochemical analysis of the pancreatic glands revealed that injection of T-cells from insulin-fed mice upregulated the number of interleukin (IL)-4-secreting cells within the islets. |
| 679 | 9421372 | Using two strains of NOD mice congenic at the Tbeta, or Thy1, locus, we observed a higher proportion of T-cells from insulin-fed mice in both the spleen (7.73 +/- 0.3 vs. 5.57 +/- 0.2%; P < 0.001) and the pancreatic lymph nodes (10.1 +/- 0.8 vs. 7.2 +/- 0.7%; P < 0.05) of cotransferred mice. |
| 680 | 9421372 | By reverse transcription-polymerase chain reaction (RT-PCR) analysis, mice reconstituted with T-cells from insulin-fed animals had detectable amounts of IL-4 mRNA, specifically in the pancreatic lymph nodes (8 of 9 experimental mice vs. 1 of 9 control mice) and the pancreas (3 of 3 experimental mice vs. 0 of 3 control mice). |
| 681 | 9421372 | Gamma-interferon mRNA was detectable in all cotransferred animals, but IL-10 mRNA and transforming growth factor beta mRNA were undetectable. |
| 682 | 9421372 | We concluded that oral administration of insulin can induce the presence of regulatory T-cells in the pancreas and the corresponding draining lymph nodes, initiate the secretion of IL-4 in this microenvironment sufficiently to suppress the activity of Th1 autoreactive T-cell clones, and ultimately provide protection against autoimmune diabetes. |
| 683 | 9421403 | Reverse transcription-PCR on pancreatic tissue revealed significantly lower levels of interferon-gamma and higher levels of interleukin-4 in the combination group. |
| 684 | 9421467 | GAD-reactive CD4+ Th1 cells induce diabetes in NOD/SCID mice. |
| 685 | 9421467 | Although glutamic acid decarboxylase (GAD) has been implicated in IDDM, there is no direct evidence showing GAD-reactive T cells are diabetogenic in vivo. |
| 686 | 9421467 | Splenocytes from this mouse showed a proliferative response to purified GAD, and were used to generate a CD4+ T cell line, designated 5A, that expresses TCRs encoding Vbeta2 and Vbeta12. 5A T cells exhibit a MHC restricted proliferative response to purified GAD, as well as GAD65 peptide 524-543. |
| 687 | 9421467 | After antigen-specific stimulation, 5A T cells secrete IFNgamma and TNFalpha/beta, but not IL-4. |
| 688 | 9421467 | We conclude that GAD injection in young NOD mice may, in some cases, provoke diabetes due to the activation of diabetogenic T cells reactive to GAD65 peptides. |
| 689 | 9421467 | Our data provide direct evidence that GAD65 autoimmunity may be a critical event in the pathogenesis of IDDM. |
| 690 | 9427742 | Mice that express influenza hemagglutinin under control of the rat insulin promoter (INS-HA) as well as a class II major histocompatibility complex (MHC)-restricted HA-specific transgenic TCR (TCR-HA), develop early insulitis with huge infiltrates, but progress late and irregularly to diabetes. |
| 691 | 9427742 | Inside the pancreas, the antigen-specific cells do not initially attack the islet cells, and produce some IFN-gamma as well as IL-10 and IL-4. |
| 692 | 9427742 | Spontaneous progression to diabetes, which can be accelerated by cyclophosphamide injection, is accompanied by a 10-fold increase in IFN-gamma and a 3-fold decrease in IL-10 and IL-4 production by the locally residing antigen-specific T cells. |
| 693 | 9427742 | Mice that express influenza hemagglutinin under control of the rat insulin promoter (INS-HA) as well as a class II major histocompatibility complex (MHC)-restricted HA-specific transgenic TCR (TCR-HA), develop early insulitis with huge infiltrates, but progress late and irregularly to diabetes. |
| 694 | 9427742 | Inside the pancreas, the antigen-specific cells do not initially attack the islet cells, and produce some IFN-gamma as well as IL-10 and IL-4. |
| 695 | 9427742 | Spontaneous progression to diabetes, which can be accelerated by cyclophosphamide injection, is accompanied by a 10-fold increase in IFN-gamma and a 3-fold decrease in IL-10 and IL-4 production by the locally residing antigen-specific T cells. |
| 696 | 9428763 | Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) is a disease controlled by the major histocompatibility complex (MHC) which results from T-cell-mediated destruction of pancreatic beta-cells. |
| 697 | 9428763 | All 56 Valpha24JalphaQ+ clones isolated from the diabetic twins/triplets secreted only interferon (IFN)-gamma upon stimulation; in contrast, 76 of 79 clones from the at-risk non-progressors and normals secreted both interleukin (IL)-4 and IFN-gamma. |
| 698 | 9428763 | Half of the at-risk non-progressors had high serum levels of IL-4 and IFN-gamma. |
| 699 | 9428763 | These results support a model for IDDM in which Thl-cell-mediated tissue damage is initially regulated by Valpha24JalphaQ+ T cells producing both cytokines; the loss of their capacity to secrete IL-4 is correlated with IDDM. |
| 700 | 9428763 | Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) is a disease controlled by the major histocompatibility complex (MHC) which results from T-cell-mediated destruction of pancreatic beta-cells. |
| 701 | 9428763 | All 56 Valpha24JalphaQ+ clones isolated from the diabetic twins/triplets secreted only interferon (IFN)-gamma upon stimulation; in contrast, 76 of 79 clones from the at-risk non-progressors and normals secreted both interleukin (IL)-4 and IFN-gamma. |
| 702 | 9428763 | Half of the at-risk non-progressors had high serum levels of IL-4 and IFN-gamma. |
| 703 | 9428763 | These results support a model for IDDM in which Thl-cell-mediated tissue damage is initially regulated by Valpha24JalphaQ+ T cells producing both cytokines; the loss of their capacity to secrete IL-4 is correlated with IDDM. |
| 704 | 9428763 | Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) is a disease controlled by the major histocompatibility complex (MHC) which results from T-cell-mediated destruction of pancreatic beta-cells. |
| 705 | 9428763 | All 56 Valpha24JalphaQ+ clones isolated from the diabetic twins/triplets secreted only interferon (IFN)-gamma upon stimulation; in contrast, 76 of 79 clones from the at-risk non-progressors and normals secreted both interleukin (IL)-4 and IFN-gamma. |
| 706 | 9428763 | Half of the at-risk non-progressors had high serum levels of IL-4 and IFN-gamma. |
| 707 | 9428763 | These results support a model for IDDM in which Thl-cell-mediated tissue damage is initially regulated by Valpha24JalphaQ+ T cells producing both cytokines; the loss of their capacity to secrete IL-4 is correlated with IDDM. |
| 708 | 9429894 | Protection from autoimmune diabetes by adjuvant therapy in the non-obese diabetic mouse: the role of interleukin-4 and interleukin-10. |
| 709 | 9429894 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by the destruction of insulin-producing beta-cells in the pancreatic islets. |
| 710 | 9429894 | Neutralizing monoclonal antibodies against IL-4 and IL-10 were injected, singularly or in combination, into CFA-treated NOD mice. |
| 711 | 9429894 | These studies suggest a role for IL-4 and IL-10 in CFA-induced protection from diabetes in the NOD mouse. |
| 712 | 9429894 | Protection from autoimmune diabetes by adjuvant therapy in the non-obese diabetic mouse: the role of interleukin-4 and interleukin-10. |
| 713 | 9429894 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by the destruction of insulin-producing beta-cells in the pancreatic islets. |
| 714 | 9429894 | Neutralizing monoclonal antibodies against IL-4 and IL-10 were injected, singularly or in combination, into CFA-treated NOD mice. |
| 715 | 9429894 | These studies suggest a role for IL-4 and IL-10 in CFA-induced protection from diabetes in the NOD mouse. |
| 716 | 9429894 | Protection from autoimmune diabetes by adjuvant therapy in the non-obese diabetic mouse: the role of interleukin-4 and interleukin-10. |
| 717 | 9429894 | Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by the destruction of insulin-producing beta-cells in the pancreatic islets. |
| 718 | 9429894 | Neutralizing monoclonal antibodies against IL-4 and IL-10 were injected, singularly or in combination, into CFA-treated NOD mice. |
| 719 | 9429894 | These studies suggest a role for IL-4 and IL-10 in CFA-induced protection from diabetes in the NOD mouse. |
| 720 | 9432975 | Continuous antigenic stimulation in vivo can result in the generation of so-called "anergic" CD4(+) or CD8(+) T cells that fail to proliferate upon antigenic stimulation and fail to develop cytolytic effector functions. |
| 721 | 9432975 | Furthermore, HA-specific T cells anergized in vivo contain higher levels of interleukin (IL)-4 messenger RNA (mRNA) than naive and recently activated T cells with the same specificity and more than a 100-fold higher levels of IL-10 mRNA. |
| 722 | 9451599 | In order to study cytokine production profile (IFN-gamma, IL-4 and TNF-alpha) and TCRBV-gene usage of peripheral autoreactive T cells from IDDM patients, we have generated antigen-specific T cell lines with either tetanus toxoid, insulinoma membranes or a single beta-cell protein, recombinant ICA69, which has been shown to be a target of both autoantibodies and T cells in IDDM. |
| 723 | 9451599 | T cell responses against beta-cell antigens and tetanus toxoid (TT) were shown to be associated with IFN-gamma and TNF-alpha production, suggestive of a Th1-like phenotype of the T-cell lines. |
| 724 | 9473384 | By measuring the cytokine production of splenic T cells after stimulation, it was shown that CD45RBlowCD4+ T cells predominantly produced IL-4 and IL-10 but produced less IL-2 and interferon-gamma (IFN-gamma). |
| 725 | 9473384 | A semiquantitative reverse-transcriptase polymerase chain reaction assay revealed a higher expression of IL-4 and IL-10 mRNA and an apparent decrease in IFN-gamma mRNA in the islets of NOD mice which were administered rIL-4. |
| 726 | 9473384 | By measuring the cytokine production of splenic T cells after stimulation, it was shown that CD45RBlowCD4+ T cells predominantly produced IL-4 and IL-10 but produced less IL-2 and interferon-gamma (IFN-gamma). |
| 727 | 9473384 | A semiquantitative reverse-transcriptase polymerase chain reaction assay revealed a higher expression of IL-4 and IL-10 mRNA and an apparent decrease in IFN-gamma mRNA in the islets of NOD mice which were administered rIL-4. |
| 728 | 9480725 | Non-obese diabetic (NOD) mice spontaneously develop insulin-dependent (type 1) diabetes mellitus (IDDM) caused by T cells which destroy the insulin-producing islet beta-cells. |
| 729 | 9480725 | Since cytokines are involved in this auto-immune beta-cell damage, we used an ELISPOT assay to enumerate the islet-associated T cells that secreted interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) or interleukin-4 (IL-4). |
| 730 | 9480725 | We found that NOD females, more susceptible than males to IDDM, accumulated islet IFN-gamma producers more rapidly with age than did the males. |
| 731 | 9480725 | Acceleration of male IDDM by cyclophosphamide led to a marked increase in IFN-gamma secreting islet T cells. |
| 732 | 9520451 | This shift in CD45 isoform expression from CD45RBHi to CD45RBLo was associated with an increase in the intragraft expression of transcripts for interleukin (IL) 4 and IL-10, consistent with the expected activity of this distinct immunoregulatory T cell subset. |
| 733 | 9529321 | alpha/beta-T cell receptor (TCR)+CD4-CD8- (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10. |
| 734 | 9529321 | We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in alpha/beta-T cell receptor (TCR)+CD4-CD8- NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). |
| 735 | 9529321 | A single intravenous injection of 10(6) CD4-/lowCD8- or CD4-CD8- thymocytes from female (BALB/c x NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. |
| 736 | 9529321 | When alpha/beta-TCR+ and alpha/beta-TCR- subsets of CD4-CD8- thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the alpha/beta-TCR+ population was protective, confirming that NKT cells were responsible for this activity. |
| 737 | 9529321 | The protective effect in the induced model of IDDM was neutralized by anti-IL-4 and anti-IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. |
| 738 | 9529321 | alpha/beta-T cell receptor (TCR)+CD4-CD8- (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10. |
| 739 | 9529321 | We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in alpha/beta-T cell receptor (TCR)+CD4-CD8- NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). |
| 740 | 9529321 | A single intravenous injection of 10(6) CD4-/lowCD8- or CD4-CD8- thymocytes from female (BALB/c x NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. |
| 741 | 9529321 | When alpha/beta-TCR+ and alpha/beta-TCR- subsets of CD4-CD8- thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the alpha/beta-TCR+ population was protective, confirming that NKT cells were responsible for this activity. |
| 742 | 9529321 | The protective effect in the induced model of IDDM was neutralized by anti-IL-4 and anti-IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. |
| 743 | 9550435 | Islet grafts and spleens from TNF-alpha-treated mice at 10 days after islet transplantation contained significantly fewer CD4+ and CD8+ T cells, and significantly decreased mRNA levels of type 1 cytokines (IFN-gamma, IL-2, and TNF-beta) than islet grafts and spleens from control mice. |
| 744 | 9550435 | Regarding type 2 cytokines, IL-4 mRNA levels were not changed significantly in islet grafts or spleens of TNF-alpha-treated mice, whereas IL-10 mRNA levels were decreased significantly in islet grafts of TNF-alpha-treated mice and not significantly changed in spleens. |
| 745 | 9550435 | TGF-beta mRNA levels in islet grafts and spleens were similar in TNF-alpha-treated and control mice. |
| 746 | 9550435 | These results suggest that TNF-alpha partially protects beta cells in syngeneic islet grafts from recurrent autoimmune destruction by reducing CD4+ and CD8+ T cells and down-regulating type 1 cytokines, both systemically and locally in the islet graft. |
| 747 | 9568689 | Inhibition of IL-12 and IFN-gamma secretion was demonstrated in macrophages activated with lipopolysaccharide or T-cells stimulated through the CD3/T-cell receptor complex, respectively. |
| 748 | 9568689 | Tumor necrosis factor-alpha was also inhibited, but IL-4 was less sensitive to suppression. |
| 749 | 9576014 | Oral administration of insulin to NOD mice suppresses or delays the onset of diabetes by skewing the response toward CD4+ Th2 cells and TGF-beta producing cells. |
| 750 | 9576014 | When cytokine profiles were examined, feeding led to a predominance of IL-10 and TGF-beta production. |
| 751 | 9576014 | Furthermore, feeding SEA in combination with insulin B-chain augmented the level of IL-10 production to insulin. |
| 752 | 9576014 | T-cell lines established from SEA-fed and -immunized mice secreted IL-4 and IL-10 cytokines whereas the T-cell lines from control-fed mice immunized with SEA secreted predominantly IL-2 and IFN-gamma. |
| 753 | 9576014 | These results demonstrate that orally administered insulin can induce regulatory T-cells secreting IL-4, IL-10, and TGF-beta and that Th2 responses to oral insulin could be augmented in a synergistic way by feeding SEA and insulin B-chain together. |
| 754 | 9576014 | Oral administration of insulin to NOD mice suppresses or delays the onset of diabetes by skewing the response toward CD4+ Th2 cells and TGF-beta producing cells. |
| 755 | 9576014 | When cytokine profiles were examined, feeding led to a predominance of IL-10 and TGF-beta production. |
| 756 | 9576014 | Furthermore, feeding SEA in combination with insulin B-chain augmented the level of IL-10 production to insulin. |
| 757 | 9576014 | T-cell lines established from SEA-fed and -immunized mice secreted IL-4 and IL-10 cytokines whereas the T-cell lines from control-fed mice immunized with SEA secreted predominantly IL-2 and IFN-gamma. |
| 758 | 9576014 | These results demonstrate that orally administered insulin can induce regulatory T-cells secreting IL-4, IL-10, and TGF-beta and that Th2 responses to oral insulin could be augmented in a synergistic way by feeding SEA and insulin B-chain together. |
| 759 | 9608925 | By altering the TNF and IL-1 cytokines, leukocytic activation can be controlled. |
| 760 | 9608925 | Other cytokines (IL-4, IL-10) have an immunosuppressive action and reduce the formation of TF. |
| 761 | 9616216 | Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4(+) T cells, interferon-gamma, and CTLA4. |
| 762 | 9616216 | (c) Induction of skin allograft acceptance initially depended on the presence of IFN-gamma, CTLA4, and CD4(+) T cells. |
| 763 | 9616216 | Addition of anti-CTLA4 or anti-IFN-gamma mAb to the protocol was associated with prompt graft rejection, whereas anti-IL-4 mAb had no effect. |
| 764 | 9619488 | CD4+ T cells may be assigned a functional status (Th1 or Th2) according to the cytokines they produce including IL-2, IFN-gamma and IL-4. |
| 765 | 9630837 | Most importantly, treatment induced higher IFN-gamma/IL-4 ratios among CD4 T cells, suggesting a strong shift toward Th1 development, perhaps through direct effects on patterns of gene expression in CD4 T cells. |
| 766 | 9679667 | Correlation studies between cytokines expressed in islets and autoimmune diabetes development in NOD mice and BB rats have demonstrated that beta-cell destructive insulitis is associated with increased expression of proinflammatory cytokines (IL-1, TNF alpha, and IFN alpha) and type 1 cytokines (IFN gamma, TNF beta, IL-2 and IL-12), whereas non-destructive (benign) insulitis is associated with increased expression of type 2 cytokines (IL-4 and IL-10) and the type 3 cytokine (TGF beta). |
| 767 | 9679667 | Cytokines (IL-1, TNF alpha, TNF beta and IFN gamma) may be directly cytotoxic to beta-cells by inducing nitric oxide and oxygen free radicals in the beta-cells. |
| 768 | 9679667 | In addition, cytokines may sensitize beta-cells to T-cell-mediated cytotoxicity in vivo by upregulating MHC class I expression on the beta-cells (an action of IFN gamma), and inducing Fas (CD95) expression on beta-cells (actions of IL-1, and possibly TNF alpha and IFN gamma). |
| 769 | 9679667 | Transgenic expression of cytokines in beta-cells of non-diabetes-prone mice and NOD mice has suggested pathogenic roles for IFN alpha, IFN gamma, IL-2 and IL-10 in insulin-dependent diabetes mellitus (IDDM) development, and protective roles for IL-4, IL-6 and TNF alpha. |
| 770 | 9679667 | Islet-reactive CD4+ T-cell lines and clones that adoptively transfer IDDM into young NOD mice have a Th1 phenotype (IFN gamma-producing), but other islet-specific Th1 clones that produce TGF beta can adoptively transfer protection against IDDM in NOD mice. |
| 771 | 9679667 | NOD mice with targeted deletions of IL-12 and IFN gamma genes still develop IDDM, albeit delayed and slightly less often. |
| 772 | 9679667 | In contrast, post-natal deletions of IL-12 and IFN gamma, also IL-1, TNF alpha, IL-2, and IL-6--by systemic administrations of neutralizing antibodies, soluble receptors and receptor antagonists, and receptor-targeted cytotoxic drugs--significantly decrease IDDM incidence in NOD mice and/or BB rats. |
| 773 | 9679667 | These cytokine deletion studies have provided the best evidence for pathologic roles for proinflammatory cytokines (IL-1, TNF alpha, and IL-6) and type 1 cytokines (IFN gamma, IL-2 and IL-12) in IDDM development. |
| 774 | 9679667 | Correlation studies between cytokines expressed in islets and autoimmune diabetes development in NOD mice and BB rats have demonstrated that beta-cell destructive insulitis is associated with increased expression of proinflammatory cytokines (IL-1, TNF alpha, and IFN alpha) and type 1 cytokines (IFN gamma, TNF beta, IL-2 and IL-12), whereas non-destructive (benign) insulitis is associated with increased expression of type 2 cytokines (IL-4 and IL-10) and the type 3 cytokine (TGF beta). |
| 775 | 9679667 | Cytokines (IL-1, TNF alpha, TNF beta and IFN gamma) may be directly cytotoxic to beta-cells by inducing nitric oxide and oxygen free radicals in the beta-cells. |
| 776 | 9679667 | In addition, cytokines may sensitize beta-cells to T-cell-mediated cytotoxicity in vivo by upregulating MHC class I expression on the beta-cells (an action of IFN gamma), and inducing Fas (CD95) expression on beta-cells (actions of IL-1, and possibly TNF alpha and IFN gamma). |
| 777 | 9679667 | Transgenic expression of cytokines in beta-cells of non-diabetes-prone mice and NOD mice has suggested pathogenic roles for IFN alpha, IFN gamma, IL-2 and IL-10 in insulin-dependent diabetes mellitus (IDDM) development, and protective roles for IL-4, IL-6 and TNF alpha. |
| 778 | 9679667 | Islet-reactive CD4+ T-cell lines and clones that adoptively transfer IDDM into young NOD mice have a Th1 phenotype (IFN gamma-producing), but other islet-specific Th1 clones that produce TGF beta can adoptively transfer protection against IDDM in NOD mice. |
| 779 | 9679667 | NOD mice with targeted deletions of IL-12 and IFN gamma genes still develop IDDM, albeit delayed and slightly less often. |
| 780 | 9679667 | In contrast, post-natal deletions of IL-12 and IFN gamma, also IL-1, TNF alpha, IL-2, and IL-6--by systemic administrations of neutralizing antibodies, soluble receptors and receptor antagonists, and receptor-targeted cytotoxic drugs--significantly decrease IDDM incidence in NOD mice and/or BB rats. |
| 781 | 9679667 | These cytokine deletion studies have provided the best evidence for pathologic roles for proinflammatory cytokines (IL-1, TNF alpha, and IL-6) and type 1 cytokines (IFN gamma, IL-2 and IL-12) in IDDM development. |
| 782 | 9699087 | Determination of mRNA expression for IFN-gamma and IL-4 in lymphocytes from children with IDDM by RT-PCR technique. |
| 783 | 9699087 | Insulin-dependent diabetes mellitus (IDDM) is characterized by infiltration of T-lymphocytes in the islets of Langerhans. |
| 784 | 9699087 | Antigens are presented to Th-lymphocytes which can be divided into Th1- and Th2-lymphocytes, producing interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) respectively. |
| 785 | 9699087 | The expression of mRNA for IL-4, and to a lesser degree IFN-gamma, is increased in lymphocytes stimulated with tetanus toxoid (TT). |
| 786 | 9699087 | In a pilot application, the lymphocytes from children with newly diagnosed IDDM were stimulated with a peptide of glutamic acid decarboxylase (GAD) (a.a. 247-279) known to have a similar aminoacid sequence as the Coxsackie B virus (a.a. 32-47). |
| 787 | 9699087 | Increased IFN-gamma mRNA could be seen in two out of four children, whereas IL-4 showed a less pronounced mRNA expression. |
| 788 | 9699087 | No increased mRNA expression for IFN-gamma and IL-4 could be seen in healthy HLA-matched controls. |
| 789 | 9699087 | Further studies are needed to confirm whether increased IFN-gamma mRNA in Th1-like lymphocytes stimulated with this specific GAD-peptide play a role in the cell-mediated immune response seen in children early after the onset of IDDM. |
| 790 | 9699087 | Determination of mRNA expression for IFN-gamma and IL-4 in lymphocytes from children with IDDM by RT-PCR technique. |
| 791 | 9699087 | Insulin-dependent diabetes mellitus (IDDM) is characterized by infiltration of T-lymphocytes in the islets of Langerhans. |
| 792 | 9699087 | Antigens are presented to Th-lymphocytes which can be divided into Th1- and Th2-lymphocytes, producing interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) respectively. |
| 793 | 9699087 | The expression of mRNA for IL-4, and to a lesser degree IFN-gamma, is increased in lymphocytes stimulated with tetanus toxoid (TT). |
| 794 | 9699087 | In a pilot application, the lymphocytes from children with newly diagnosed IDDM were stimulated with a peptide of glutamic acid decarboxylase (GAD) (a.a. 247-279) known to have a similar aminoacid sequence as the Coxsackie B virus (a.a. 32-47). |
| 795 | 9699087 | Increased IFN-gamma mRNA could be seen in two out of four children, whereas IL-4 showed a less pronounced mRNA expression. |
| 796 | 9699087 | No increased mRNA expression for IFN-gamma and IL-4 could be seen in healthy HLA-matched controls. |
| 797 | 9699087 | Further studies are needed to confirm whether increased IFN-gamma mRNA in Th1-like lymphocytes stimulated with this specific GAD-peptide play a role in the cell-mediated immune response seen in children early after the onset of IDDM. |
| 798 | 9699087 | Determination of mRNA expression for IFN-gamma and IL-4 in lymphocytes from children with IDDM by RT-PCR technique. |
| 799 | 9699087 | Insulin-dependent diabetes mellitus (IDDM) is characterized by infiltration of T-lymphocytes in the islets of Langerhans. |
| 800 | 9699087 | Antigens are presented to Th-lymphocytes which can be divided into Th1- and Th2-lymphocytes, producing interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) respectively. |
| 801 | 9699087 | The expression of mRNA for IL-4, and to a lesser degree IFN-gamma, is increased in lymphocytes stimulated with tetanus toxoid (TT). |
| 802 | 9699087 | In a pilot application, the lymphocytes from children with newly diagnosed IDDM were stimulated with a peptide of glutamic acid decarboxylase (GAD) (a.a. 247-279) known to have a similar aminoacid sequence as the Coxsackie B virus (a.a. 32-47). |
| 803 | 9699087 | Increased IFN-gamma mRNA could be seen in two out of four children, whereas IL-4 showed a less pronounced mRNA expression. |
| 804 | 9699087 | No increased mRNA expression for IFN-gamma and IL-4 could be seen in healthy HLA-matched controls. |
| 805 | 9699087 | Further studies are needed to confirm whether increased IFN-gamma mRNA in Th1-like lymphocytes stimulated with this specific GAD-peptide play a role in the cell-mediated immune response seen in children early after the onset of IDDM. |
| 806 | 9699087 | Determination of mRNA expression for IFN-gamma and IL-4 in lymphocytes from children with IDDM by RT-PCR technique. |
| 807 | 9699087 | Insulin-dependent diabetes mellitus (IDDM) is characterized by infiltration of T-lymphocytes in the islets of Langerhans. |
| 808 | 9699087 | Antigens are presented to Th-lymphocytes which can be divided into Th1- and Th2-lymphocytes, producing interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) respectively. |
| 809 | 9699087 | The expression of mRNA for IL-4, and to a lesser degree IFN-gamma, is increased in lymphocytes stimulated with tetanus toxoid (TT). |
| 810 | 9699087 | In a pilot application, the lymphocytes from children with newly diagnosed IDDM were stimulated with a peptide of glutamic acid decarboxylase (GAD) (a.a. 247-279) known to have a similar aminoacid sequence as the Coxsackie B virus (a.a. 32-47). |
| 811 | 9699087 | Increased IFN-gamma mRNA could be seen in two out of four children, whereas IL-4 showed a less pronounced mRNA expression. |
| 812 | 9699087 | No increased mRNA expression for IFN-gamma and IL-4 could be seen in healthy HLA-matched controls. |
| 813 | 9699087 | Further studies are needed to confirm whether increased IFN-gamma mRNA in Th1-like lymphocytes stimulated with this specific GAD-peptide play a role in the cell-mediated immune response seen in children early after the onset of IDDM. |
| 814 | 9699087 | Determination of mRNA expression for IFN-gamma and IL-4 in lymphocytes from children with IDDM by RT-PCR technique. |
| 815 | 9699087 | Insulin-dependent diabetes mellitus (IDDM) is characterized by infiltration of T-lymphocytes in the islets of Langerhans. |
| 816 | 9699087 | Antigens are presented to Th-lymphocytes which can be divided into Th1- and Th2-lymphocytes, producing interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) respectively. |
| 817 | 9699087 | The expression of mRNA for IL-4, and to a lesser degree IFN-gamma, is increased in lymphocytes stimulated with tetanus toxoid (TT). |
| 818 | 9699087 | In a pilot application, the lymphocytes from children with newly diagnosed IDDM were stimulated with a peptide of glutamic acid decarboxylase (GAD) (a.a. 247-279) known to have a similar aminoacid sequence as the Coxsackie B virus (a.a. 32-47). |
| 819 | 9699087 | Increased IFN-gamma mRNA could be seen in two out of four children, whereas IL-4 showed a less pronounced mRNA expression. |
| 820 | 9699087 | No increased mRNA expression for IFN-gamma and IL-4 could be seen in healthy HLA-matched controls. |
| 821 | 9699087 | Further studies are needed to confirm whether increased IFN-gamma mRNA in Th1-like lymphocytes stimulated with this specific GAD-peptide play a role in the cell-mediated immune response seen in children early after the onset of IDDM. |
| 822 | 9712353 | Pancreatic islet beta cell destruction leading to insulin-dependent diabetes mellitus (IDDM) is believed to be mediated by a T-helper 1 (T(H)1) lymphocyte response to islet antigens. |
| 823 | 9712353 | In the mouse, T(H)1 (IL-2, IFN-gamma) and T(H)2 (IL-4, -5, -6, -10) responses are associated with the generation of IgG2a and IgG1 subclasses, respectively. |
| 824 | 9712353 | Because the IgG subclass response to an antigen may be a potentially useful marker of T(H)1/T(H)2 immune balance we measured IgG subclass antibodies to glutamic acid decarboxylase (GAD), a major islet autoantigen in IDDM, in 34 newly-diagnosed IDDM patients and in 28 at-risk, first-degree relatives of people with IDDM. |
| 825 | 9719467 | Insulin-dependent diabetes mellitus (IDDM) is a disease that results from autoimmune destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans. |
| 826 | 9719467 | Type 1 cytokines--interleukin 2 (IL-2), interferon gamma (IFNgamma), and tumor necrosis factor beta (TNFbeta), dominate over an immunoregulatory (suppressor) Th2 subset of T cells and their cytokine products, i.e. |
| 827 | 9719467 | Type 2 cytokines--IL-4 and IL-10. |
| 828 | 9719467 | Type 1 cytokines activate (1) cytotoxic T cells that interact specifically with beta-cells and destroy them, and (2) macrophages to produce proinflammatory cytokines (IL-1 and TNFalpha), and oxygen and nitrogen free radicals that are highly toxic to islet beta-cells. |
| 829 | 9719467 | Furthermore, the cytokines IL-1, TNFalpha, and IFNgamma are cytotoxic to beta-cells, in large part by inducing the formation of oxygen free radicals, nitric oxide, and peroxynitrite in the beta-cells themselves. |
| 830 | 9725204 | Autoimmunity without diabetes in transgenic mice expressing beta cell-specific CD86, but not CD80: parameters that trigger progression to diabetes. |
| 831 | 9725204 | To define more clearly the roles of CD80 (RIP-CD80) and CD86 (RIP-CD86) in the activation of autoreactive T cells in vivo, we generated transgenic mice expressing either or both costimulatory molecules on the beta cells of the pancreas. |
| 832 | 9725204 | While RIP-CD80 mice do not show any sign of autoimmunity, at the age of 7 mo RIP-CD86 transgenic mice develop a lymphoid infiltrate with both IFN-gamma- and IL-4-positive cells in the vicinity of the islets; these mice, however, never progress to diabetes. |
| 833 | 9725204 | This fundamental difference in the ability of CD80 and CD86 to activate self-reactive T cells in vivo is, however, obliterated when the level of TCR signaling is increased by either TNF-alpha or transgenic MHC class II expression. |
| 834 | 9725204 | These results support the suggestion that CD80 and CD86 mainly differ at the level of the intensity of the signals they deliver. |
| 835 | 9726227 | This clearly demonstrates that transient inactivation of most T-cells with anti-CD4 plus anti-CD8 mAbs effectively controls autoimmune disease in the isograft, despite recovery of CD4 and CD8 T-cells to normal levels. |
| 836 | 9726227 | Histology showed a predominantly peri-islet T-cell and macrophage infiltrate with ductal expression of the cytokines interleukin (IL)-4, IL-2, and interferon-gamma. |
| 837 | 9753294 | Susceptibility to the human autoimmune disease IDDM is strongly associated with those haplotypes of the major histocompatibility complex (MHC) carrying DQB1 alleles that do not encode aspartic acid at codon 57. |
| 838 | 9753294 | This inhibition was partially reversed by treatment of the recipients with a combination of anti-interleukin (IL)-4 and anti-IL-10 monoclonal antibodies. |
| 839 | 9753294 | Thus, a transgenic class II MHC allele encoding aspartic acid at B57 prevents diabetes, in part, by promoting the production of IL-4 and IL-10, which interfere with the effector phase of the diabetic process. |
| 840 | 9753294 | Susceptibility to the human autoimmune disease IDDM is strongly associated with those haplotypes of the major histocompatibility complex (MHC) carrying DQB1 alleles that do not encode aspartic acid at codon 57. |
| 841 | 9753294 | This inhibition was partially reversed by treatment of the recipients with a combination of anti-interleukin (IL)-4 and anti-IL-10 monoclonal antibodies. |
| 842 | 9753294 | Thus, a transgenic class II MHC allele encoding aspartic acid at B57 prevents diabetes, in part, by promoting the production of IL-4 and IL-10, which interfere with the effector phase of the diabetic process. |
| 843 | 9761385 | Decreased in vitro IL-4 [corrected] and IL-10 production by peripheral blood in first degree relatives at high risk of diabetes type-I. |
| 844 | 9761385 | The aim of the present study was the estimation of in vitro production of Th1 (INF-gamma, IL-2) and Th2-derived (IL-4, IL-10) cytokines by peripheral blood in ICA and GADA positive first degree relatives of Type-I diabetes patients, since they could represent primary events triggering an immune-mediated islets destruction. |
| 845 | 9761385 | In subjects at increased risk of Type-I diabetes, levels of IL-4 positively correlated with those of IL-10. |
| 846 | 9761385 | In conclusion our study has shown decreased IL-4 and IL-10 production, but normal secretion of Th1-derived cytokines by peripheral blood of prediabetic humans. |
| 847 | 9761385 | Decreased in vitro IL-4 [corrected] and IL-10 production by peripheral blood in first degree relatives at high risk of diabetes type-I. |
| 848 | 9761385 | The aim of the present study was the estimation of in vitro production of Th1 (INF-gamma, IL-2) and Th2-derived (IL-4, IL-10) cytokines by peripheral blood in ICA and GADA positive first degree relatives of Type-I diabetes patients, since they could represent primary events triggering an immune-mediated islets destruction. |
| 849 | 9761385 | In subjects at increased risk of Type-I diabetes, levels of IL-4 positively correlated with those of IL-10. |
| 850 | 9761385 | In conclusion our study has shown decreased IL-4 and IL-10 production, but normal secretion of Th1-derived cytokines by peripheral blood of prediabetic humans. |
| 851 | 9761385 | Decreased in vitro IL-4 [corrected] and IL-10 production by peripheral blood in first degree relatives at high risk of diabetes type-I. |
| 852 | 9761385 | The aim of the present study was the estimation of in vitro production of Th1 (INF-gamma, IL-2) and Th2-derived (IL-4, IL-10) cytokines by peripheral blood in ICA and GADA positive first degree relatives of Type-I diabetes patients, since they could represent primary events triggering an immune-mediated islets destruction. |
| 853 | 9761385 | In subjects at increased risk of Type-I diabetes, levels of IL-4 positively correlated with those of IL-10. |
| 854 | 9761385 | In conclusion our study has shown decreased IL-4 and IL-10 production, but normal secretion of Th1-derived cytokines by peripheral blood of prediabetic humans. |
| 855 | 9761385 | Decreased in vitro IL-4 [corrected] and IL-10 production by peripheral blood in first degree relatives at high risk of diabetes type-I. |
| 856 | 9761385 | The aim of the present study was the estimation of in vitro production of Th1 (INF-gamma, IL-2) and Th2-derived (IL-4, IL-10) cytokines by peripheral blood in ICA and GADA positive first degree relatives of Type-I diabetes patients, since they could represent primary events triggering an immune-mediated islets destruction. |
| 857 | 9761385 | In subjects at increased risk of Type-I diabetes, levels of IL-4 positively correlated with those of IL-10. |
| 858 | 9761385 | In conclusion our study has shown decreased IL-4 and IL-10 production, but normal secretion of Th1-derived cytokines by peripheral blood of prediabetic humans. |
| 859 | 9767450 | We have used these transgenic NOD mice, together with non-transgenic NOD mice, to study the correlation of E expression and production of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). |
| 860 | 9776711 | Glutamic acid decarboxylase autoimmunity was investigated by immunizing female BALB/c, C57B1/6, National Marine Research Institute (NMRI) and non-obese diabetic (NOD) mice once or twice with glumatic acid decarboxylase, GAD65, bovine serum albumin, or phosphate-buffered saline in incomplete Freunds adjuvant, or not treating. |
| 861 | 9776711 | Mice immunized with GAD65, showed splinic T-cell reactivity to GAD 65 in vitro assessed by cytokine secretion. |
| 862 | 9776711 | IL-4 and IL-10 were only detected after two immunizations with higher levels in BALB/c, NMRI and NOD mice, compared to C57B1/6 mice. |
| 863 | 9776711 | In NOD mice, peri-insulitis was detected in all groups, but less so in GAD65 and bovine serum albumin (BSA) immunized animals. |
| 864 | 9780163 | In pCMV-TGF-beta1-treated mice, pancreatic IL-12 and IFN-gamma mRNA expression was depressed, and the ratio of IFN-gamma to IL-4 mRNA was decreased, as determined by semiquantitative reverse-transcription PCR. |
| 865 | 9794112 | It increased the concanavalin A and ionomycin plus myristic acid palmitic ester-induced production of interleukin 4 and 10 and interferon gamma-secretion in spleen cells from treated mice. |
| 866 | 9794112 | Adoptive transfer of unstimulated splenocytes secreting interleukin 4 and interleukin 10 from fed interferon alpha donors suppressed spontaneous diabetes mellitus in recipients. |
| 867 | 9794112 | The protective effect of adoptively transferred unstimulated splenocytes shows the presence of ingested interferon alpha-activated regulatory splenic cell populations that may work via increased interleukin 4 or interleukin 10 production. |
| 868 | 9794112 | It increased the concanavalin A and ionomycin plus myristic acid palmitic ester-induced production of interleukin 4 and 10 and interferon gamma-secretion in spleen cells from treated mice. |
| 869 | 9794112 | Adoptive transfer of unstimulated splenocytes secreting interleukin 4 and interleukin 10 from fed interferon alpha donors suppressed spontaneous diabetes mellitus in recipients. |
| 870 | 9794112 | The protective effect of adoptively transferred unstimulated splenocytes shows the presence of ingested interferon alpha-activated regulatory splenic cell populations that may work via increased interleukin 4 or interleukin 10 production. |
| 871 | 9794112 | It increased the concanavalin A and ionomycin plus myristic acid palmitic ester-induced production of interleukin 4 and 10 and interferon gamma-secretion in spleen cells from treated mice. |
| 872 | 9794112 | Adoptive transfer of unstimulated splenocytes secreting interleukin 4 and interleukin 10 from fed interferon alpha donors suppressed spontaneous diabetes mellitus in recipients. |
| 873 | 9794112 | The protective effect of adoptively transferred unstimulated splenocytes shows the presence of ingested interferon alpha-activated regulatory splenic cell populations that may work via increased interleukin 4 or interleukin 10 production. |
| 874 | 9799714 | CD1-restricted T cells are frequently autoreactive, and can promptly release key regulatory cytokines such as IL-4 and IFN-gamma. |
| 875 | 9840449 | Peptide from glutamic acid decarboxylase similar to coxsackie B virus stimulates IFN-gamma mRNA expression in Th1-like lymphocytes from children with recent-onset insulin-dependent diabetes mellitus. |
| 876 | 9840449 | CD4+ or Th-lymphocytes will be activated after stimulation resulting in interferon-gamma (IFN-gamma) production by Th1-like lymphocytes and/or interleukin-4 (IL-4) secretion from Th2-like lymphocytes. |
| 877 | 9840449 | In this study we have shown that this peptide activates Th1-like lymphocytes which produce increased amounts of IFN-gamma mRNA, but seldom mRNA for IL-4. |
| 878 | 9840449 | In conclusion, we suggest that GAD65 is involved in the development of type 1 diabetes and that the Th1-response may play a role in the destruction of beta cells. |
| 879 | 9840449 | Peptide from glutamic acid decarboxylase similar to coxsackie B virus stimulates IFN-gamma mRNA expression in Th1-like lymphocytes from children with recent-onset insulin-dependent diabetes mellitus. |
| 880 | 9840449 | CD4+ or Th-lymphocytes will be activated after stimulation resulting in interferon-gamma (IFN-gamma) production by Th1-like lymphocytes and/or interleukin-4 (IL-4) secretion from Th2-like lymphocytes. |
| 881 | 9840449 | In this study we have shown that this peptide activates Th1-like lymphocytes which produce increased amounts of IFN-gamma mRNA, but seldom mRNA for IL-4. |
| 882 | 9840449 | In conclusion, we suggest that GAD65 is involved in the development of type 1 diabetes and that the Th1-response may play a role in the destruction of beta cells. |
| 883 | 9878081 | Since autoimmune responses to glutamic acid decarboxylase (GAD) are up-regulated in insulin-dependent diabetes mellitus (IDDM), in this study GAD67-specific antibody, T cell proliferation and lymphokine production patterns were analysed in the adjuvant-treated mice to characterize the regulatory mechanisms underlying the protection. |
| 884 | 9878081 | Upon in vitro stimulation with GAD67, draining lymph node and spleen cells from CFA-immunized NOD mice or syngeneic islet-grafted and BCG-protected NOD mice produced much more IL-4, whereas there was no significant change in IFN-gamma production. |
| 885 | 9878085 | Therefore, we examined the peak levels, secretory pattern and total cytokine production (calculated as the area under the curve, AUC) of the Th1 cytokines, IL-2 and IFN-gamma, and Th2 cytokines, IL-4 and IL-10, from stimulated peripheral blood mononuclear cells, from 17 IDDM patients and 24 normal controls. |
| 886 | 9878085 | This resulted in significant differences in secretory patterns of IFN-gammaIL-2, IL-4 and IL-10 between the two groups; P<0.001, P<0.005, P<0.005 and P<0.001, respectively. |
| 887 | 9878085 | No correlation was found in the diabetic patients between any profiles of the cytokines and their various clinical parameters, including age, gender, disease duration, insulin requirements or glycated hemoglobin levels. |
| 888 | 9878085 | Therefore, we examined the peak levels, secretory pattern and total cytokine production (calculated as the area under the curve, AUC) of the Th1 cytokines, IL-2 and IFN-gamma, and Th2 cytokines, IL-4 and IL-10, from stimulated peripheral blood mononuclear cells, from 17 IDDM patients and 24 normal controls. |
| 889 | 9878085 | This resulted in significant differences in secretory patterns of IFN-gammaIL-2, IL-4 and IL-10 between the two groups; P<0.001, P<0.005, P<0.005 and P<0.001, respectively. |
| 890 | 9878085 | No correlation was found in the diabetic patients between any profiles of the cytokines and their various clinical parameters, including age, gender, disease duration, insulin requirements or glycated hemoglobin levels. |
| 891 | 9892610 | Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor beta and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC- cells and CD4(+)CD8(-) thymocytes. |
| 892 | 9892610 | Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation of PVG.RT1(u) rats can be prevented by their reconstitution with peripheral CD4(+)CD45RC-TCR-alpha/beta+RT6(+) cells and CD4(+)CD8(-) thymocytes from normal syngeneic donors. |
| 893 | 9892610 | RT1(u) rats, development of thyroiditis was prevented by the transfer of CD4(+)CD45RC- and CD4(+)CD8(-) thymocytes from normal donors but not by CD4(+)CD45RC+ peripheral T cells. |
| 894 | 9892610 | We now show that transforming growth factor (TGF)-beta and interleukin (IL)-4 both play essential roles in the mechanism of this protection since administration of monoclonal antibodies that block the biological activity of either of these cytokines abrogates the protective effect of the donor cells in the recipient rats. |
| 895 | 9892610 | The prevention of both diabetes and thyroiditis by CD4(+)CD45RC- peripheral cells and CD4(+)CD8(-) thymocytes therefore does not support the view that the mechanism of regulation involves a switch from a T helper cell type 1 (Th1) to a Th2-like response, but rather relies upon a specific suppression of the autoimmune responses involving TGF-beta and IL-4. |
| 896 | 9892610 | Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor beta and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC- cells and CD4(+)CD8(-) thymocytes. |
| 897 | 9892610 | Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation of PVG.RT1(u) rats can be prevented by their reconstitution with peripheral CD4(+)CD45RC-TCR-alpha/beta+RT6(+) cells and CD4(+)CD8(-) thymocytes from normal syngeneic donors. |
| 898 | 9892610 | RT1(u) rats, development of thyroiditis was prevented by the transfer of CD4(+)CD45RC- and CD4(+)CD8(-) thymocytes from normal donors but not by CD4(+)CD45RC+ peripheral T cells. |
| 899 | 9892610 | We now show that transforming growth factor (TGF)-beta and interleukin (IL)-4 both play essential roles in the mechanism of this protection since administration of monoclonal antibodies that block the biological activity of either of these cytokines abrogates the protective effect of the donor cells in the recipient rats. |
| 900 | 9892610 | The prevention of both diabetes and thyroiditis by CD4(+)CD45RC- peripheral cells and CD4(+)CD8(-) thymocytes therefore does not support the view that the mechanism of regulation involves a switch from a T helper cell type 1 (Th1) to a Th2-like response, but rather relies upon a specific suppression of the autoimmune responses involving TGF-beta and IL-4. |
| 901 | 9892610 | Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor beta and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC- cells and CD4(+)CD8(-) thymocytes. |
| 902 | 9892610 | Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation of PVG.RT1(u) rats can be prevented by their reconstitution with peripheral CD4(+)CD45RC-TCR-alpha/beta+RT6(+) cells and CD4(+)CD8(-) thymocytes from normal syngeneic donors. |
| 903 | 9892610 | RT1(u) rats, development of thyroiditis was prevented by the transfer of CD4(+)CD45RC- and CD4(+)CD8(-) thymocytes from normal donors but not by CD4(+)CD45RC+ peripheral T cells. |
| 904 | 9892610 | We now show that transforming growth factor (TGF)-beta and interleukin (IL)-4 both play essential roles in the mechanism of this protection since administration of monoclonal antibodies that block the biological activity of either of these cytokines abrogates the protective effect of the donor cells in the recipient rats. |
| 905 | 9892610 | The prevention of both diabetes and thyroiditis by CD4(+)CD45RC- peripheral cells and CD4(+)CD8(-) thymocytes therefore does not support the view that the mechanism of regulation involves a switch from a T helper cell type 1 (Th1) to a Th2-like response, but rather relies upon a specific suppression of the autoimmune responses involving TGF-beta and IL-4. |
| 906 | 9933449 | Mechanisms of Mycobacterium avium-induced resistance against insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice: role of Fas and Th1 cells. |
| 907 | 9933449 | Here, we investigate whether the M. avium-induced protection of NOD mice from diabetes was associated with changes in the expression of Fas (CD95) and FasL by immune cells, as well as alterations in cytotoxic activity, interferon-gamma (IFN-gamma) and IL-4 production and activation of T cells of infected animals. |
| 908 | 10047431 | Both CD4(+)and CD8(+)T cells are required for IFN-gamma gene expression in pancreatic islets and autoimmune diabetes development in biobreeding rats. |
| 909 | 10047431 | To study the relative roles of CD4(+)and CD8(+)T cells and their cytokine products in autoimmune diabetes development, we selectively depleted CD4(+)and CD8(+)T cells in autoimmune diabetes-prone (DP) biobreeding (BB) rats, by administrations of anti-CD2 and anti-CD8 monoclonal antibody (mAb) respectively. |
| 910 | 10047431 | Depletion of CD4(+)T cells (by anti-CD2 mAb) in blood, spleen and islets prevented diabetes development in DP-BB rats, and depletion of CD8(+)T cells (by anti-CD8 mAb) delayed and significantly decreased diabetes incidence. |
| 911 | 10047431 | Depletion of either CD4(+)or CD8(+)T cells completely prevented IFN-gamma mRNA upregulation in islets of DP-BB rats above the low level expressed in islets of diabetes-resistant (DR) BB rats. |
| 912 | 10047431 | Also, IL-10 mRNA levels in islets of DP-BB rats were significantly decreased by depletion of either CD4(+)or CD8(+)T cells, whereas the effects of the anti-T cell mAb on mRNA levels of other cytokines in islets (IL-2, IL-4, IL-12p40, and TNF-alpha) were discordant. |
| 913 | 10047431 | In contrast, both mAb treatments significantly upregulated IL-4 and TNF-alpha mRNA levels in spleens of DP-BB rats. |
| 914 | 10047431 | These results demonstrate that islet infiltration by both CD4(+)and CD8(+)T cells is required for IFN-gamma and IL-10 production in islets and beta-cell destruction. |
| 915 | 10047431 | Depletion of either CD4(+)or CD8(+)T cells may prevent beta-cell destruction by decreasing IFN-gamma and IL-10 production in islets and increasing IL-4 and TNF-alpha production systemically. |
| 916 | 10047431 | Both CD4(+)and CD8(+)T cells are required for IFN-gamma gene expression in pancreatic islets and autoimmune diabetes development in biobreeding rats. |
| 917 | 10047431 | To study the relative roles of CD4(+)and CD8(+)T cells and their cytokine products in autoimmune diabetes development, we selectively depleted CD4(+)and CD8(+)T cells in autoimmune diabetes-prone (DP) biobreeding (BB) rats, by administrations of anti-CD2 and anti-CD8 monoclonal antibody (mAb) respectively. |
| 918 | 10047431 | Depletion of CD4(+)T cells (by anti-CD2 mAb) in blood, spleen and islets prevented diabetes development in DP-BB rats, and depletion of CD8(+)T cells (by anti-CD8 mAb) delayed and significantly decreased diabetes incidence. |
| 919 | 10047431 | Depletion of either CD4(+)or CD8(+)T cells completely prevented IFN-gamma mRNA upregulation in islets of DP-BB rats above the low level expressed in islets of diabetes-resistant (DR) BB rats. |
| 920 | 10047431 | Also, IL-10 mRNA levels in islets of DP-BB rats were significantly decreased by depletion of either CD4(+)or CD8(+)T cells, whereas the effects of the anti-T cell mAb on mRNA levels of other cytokines in islets (IL-2, IL-4, IL-12p40, and TNF-alpha) were discordant. |
| 921 | 10047431 | In contrast, both mAb treatments significantly upregulated IL-4 and TNF-alpha mRNA levels in spleens of DP-BB rats. |
| 922 | 10047431 | These results demonstrate that islet infiltration by both CD4(+)and CD8(+)T cells is required for IFN-gamma and IL-10 production in islets and beta-cell destruction. |
| 923 | 10047431 | Depletion of either CD4(+)or CD8(+)T cells may prevent beta-cell destruction by decreasing IFN-gamma and IL-10 production in islets and increasing IL-4 and TNF-alpha production systemically. |
| 924 | 10047431 | Both CD4(+)and CD8(+)T cells are required for IFN-gamma gene expression in pancreatic islets and autoimmune diabetes development in biobreeding rats. |
| 925 | 10047431 | To study the relative roles of CD4(+)and CD8(+)T cells and their cytokine products in autoimmune diabetes development, we selectively depleted CD4(+)and CD8(+)T cells in autoimmune diabetes-prone (DP) biobreeding (BB) rats, by administrations of anti-CD2 and anti-CD8 monoclonal antibody (mAb) respectively. |
| 926 | 10047431 | Depletion of CD4(+)T cells (by anti-CD2 mAb) in blood, spleen and islets prevented diabetes development in DP-BB rats, and depletion of CD8(+)T cells (by anti-CD8 mAb) delayed and significantly decreased diabetes incidence. |
| 927 | 10047431 | Depletion of either CD4(+)or CD8(+)T cells completely prevented IFN-gamma mRNA upregulation in islets of DP-BB rats above the low level expressed in islets of diabetes-resistant (DR) BB rats. |
| 928 | 10047431 | Also, IL-10 mRNA levels in islets of DP-BB rats were significantly decreased by depletion of either CD4(+)or CD8(+)T cells, whereas the effects of the anti-T cell mAb on mRNA levels of other cytokines in islets (IL-2, IL-4, IL-12p40, and TNF-alpha) were discordant. |
| 929 | 10047431 | In contrast, both mAb treatments significantly upregulated IL-4 and TNF-alpha mRNA levels in spleens of DP-BB rats. |
| 930 | 10047431 | These results demonstrate that islet infiltration by both CD4(+)and CD8(+)T cells is required for IFN-gamma and IL-10 production in islets and beta-cell destruction. |
| 931 | 10047431 | Depletion of either CD4(+)or CD8(+)T cells may prevent beta-cell destruction by decreasing IFN-gamma and IL-10 production in islets and increasing IL-4 and TNF-alpha production systemically. |
| 932 | 10049952 | Development of disease can be prevented by reconstitution of PVG rats shortly after their final irradiation with either peripheral CD4(+)CD45RC- T cells or CD4(+)CD8(-) thymocytes from syngeneic donors. |
| 933 | 10049952 | Although the activity of both populations is known to depend on the activities of endogenously produced interleukin 4 and transforming growth factor beta, implying a common mechanism, the issue of antigen specificity of the cells involved has not yet been addressed. |
| 934 | 10049952 | Significantly, in contrast to the peripheral CD4(+) T cells, CD4(+)CD8(-) thymocytes from 131I-treated PVG donors were still able to prevent thyroiditis upon adoptive transfer. |
| 935 | 10066341 | Secretion of IL-4 was dramatically reduced; however, secretion of IL-2 or IFN-gamma was not significantly inhibited. |
| 936 | 10066341 | Levels of mRNA encoding IFN-gamma were similar, but the appearance was delayed in thymocytes derived from STZ-treated mice, implying differential regulation of IL-4 and IFN-gamma. |
| 937 | 10066341 | Defective thymocyte proliferation was partially restored by exposure to IL-2 in vitro; however, IL-4 completely reversed the STZ-induced defect. |
| 938 | 10066341 | Secretion of IL-4 was dramatically reduced; however, secretion of IL-2 or IFN-gamma was not significantly inhibited. |
| 939 | 10066341 | Levels of mRNA encoding IFN-gamma were similar, but the appearance was delayed in thymocytes derived from STZ-treated mice, implying differential regulation of IL-4 and IFN-gamma. |
| 940 | 10066341 | Defective thymocyte proliferation was partially restored by exposure to IL-2 in vitro; however, IL-4 completely reversed the STZ-induced defect. |
| 941 | 10066341 | Secretion of IL-4 was dramatically reduced; however, secretion of IL-2 or IFN-gamma was not significantly inhibited. |
| 942 | 10066341 | Levels of mRNA encoding IFN-gamma were similar, but the appearance was delayed in thymocytes derived from STZ-treated mice, implying differential regulation of IL-4 and IFN-gamma. |
| 943 | 10066341 | Defective thymocyte proliferation was partially restored by exposure to IL-2 in vitro; however, IL-4 completely reversed the STZ-induced defect. |
| 944 | 10076185 | Moreover it significantly decreased MHC class II expression (but not class I) in vivo by week 10, and significantly enhanced intercellular adhesion molecule-1 (ICAM-1) expression, mainly by week 25, within the pancreas, where 5-bromo-2'-deoxyuridine positive nuclei and insulin positive cells were present, demonstrating that a stimulation of endocrine cell proliferation occurs. (3) In addition, NIC partly counteracted the fall of superoxide dismutase levels, observed in untreated diabetic NOD animals. (4) In vitro studies demonstrated that NIC: (i) was able to significantly reduce nitrite accumulation and to increase NAD+NADH content significantly, and (ii) was able to increase the levels of interleukin-4, a T helper 2 lymphocyte (Th2) protective cytokine, and of interferon-alpha (IFN-alpha), which is known to be able to induce MHC class I and ICAM-1 but not MHC class II expression, as well as IFN-gamma, which is also known to be able to induce MHC class I and ICAM-1 expression. |
| 945 | 10193314 | We used reverse transcriptase polymerase chain reaction (PCR) and quantitative PCR techniques to examine mRNA expression of interferon (IFN)-gamma (Th1 type cytokine), and interleukin (IL)-4 (Th2 type cytokine) in splenic cells. |
| 946 | 10193314 | We observed that in Reo-2 infected mice the level of IFN-gamma expression increases with the development of insulitis, whereas expression of message for IL-4 is minimal to detectable with the immuno-inflammatory process 10 days after infection. |
| 947 | 10193314 | Furthermore altered CD4+/CD8+ cell ratio compared with uninfected mice in the splenic cells by the infection was recovered to the ratio of uninfected mice by the treatment of mAb against mouse IFN-gamma, suggesting normalization of T cell balance in immune system. |
| 948 | 10193314 | We used reverse transcriptase polymerase chain reaction (PCR) and quantitative PCR techniques to examine mRNA expression of interferon (IFN)-gamma (Th1 type cytokine), and interleukin (IL)-4 (Th2 type cytokine) in splenic cells. |
| 949 | 10193314 | We observed that in Reo-2 infected mice the level of IFN-gamma expression increases with the development of insulitis, whereas expression of message for IL-4 is minimal to detectable with the immuno-inflammatory process 10 days after infection. |
| 950 | 10193314 | Furthermore altered CD4+/CD8+ cell ratio compared with uninfected mice in the splenic cells by the infection was recovered to the ratio of uninfected mice by the treatment of mAb against mouse IFN-gamma, suggesting normalization of T cell balance in immune system. |
| 951 | 10201899 | p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells. |
| 952 | 10201899 | In contrast to that reported for human Jurkat T cells, we found that p38 MAPK, but not Jun NH2-terminal kinase (JNK), is weakly activated upon stimulation with either anti-CD3 or anti-CD28 in murine thymocytes and splenic T cells. |
| 953 | 10201899 | However, p38 MAPK is activated strongly and synergistically by either CD3/CD28 coligation or PMA/Ca2+ ionophore stimulation, which mimics TCR-CD3/CD28-mediated signaling. |
| 954 | 10201899 | Activation of p38 MAPK correlates closely with the stimulation of T cell proliferation. |
| 955 | 10201899 | T cell proliferation and production of IL-2, IL-4, and IFN-gamma induced by both CD3 and CD3/CD28 ligation and the nuclear expression of the c-Jun and ATF-2 proteins are each blocked by the p38 MAPK inhibitor SB203580. |
| 956 | 10201899 | Our findings demonstrate that p38 MAPK 1) plays an important role in signal integration during costimulation of primary mouse T cells, 2) may be involved in the induction of c-Jun activation and augmentation of AP-1 transcriptional activity, and 3) regulates whether T cells enter a state of functional unresponsiveness. |
| 957 | 10202001 | One segregates as a recessive trait and is associated with a reduction in the peripheral frequency of diabetogenic CD8+ (but not CD4+) T cells. |
| 958 | 10202001 | The other segregates as a dominant trait and is mediated by IL-4- and TGF-beta1-independent immune suppressive functions provided by lymphocytes that target diabetogenic CD4+ and CD8+ T cells, without causing their deletion, anergy, immune deviation, or ignorance. |
| 959 | 10202048 | These changes occurred contemporaneously with a shift in the profile of circulating cytokines from a Th1-dominant (IFN-gamma) to Th2-dominant (IL-4, IL-10) phenotype. |
| 960 | 10202048 | No significant changes in either circulating IL-1beta, IL-6, or TNF-alpha levels were observed in infected mice. |
| 961 | 10230696 | We investigated whether cytokines produced primarily by monocytes/macrophages (IL-1alpha), Th1-lymphocytes (IFNgamma), or Th2-lymphocytes (IL-4) are modulated in diabetes-prone NOD mice by insulin treatment as used in prophylaxis studies. |
| 962 | 10230696 | IL-1alpha, IFNgamma and IL-4 were generally below detection in plasma of prediabetic animals and controls. |
| 963 | 10230696 | Supernatants of activated splenocytes from prediabetic NOD mice had lower levels of IL-4 (<15 pg/10(6) cells) compared with those from BALB/c mice (88+/-22 pg/10(6) cells; p<0.01), and this deficiency was partially compensated for when the NOD mice were given insulin (27+/-8; p<0.01). |
| 964 | 10230696 | The levels of IFNgamma were comparable and largely unaffected by insulin treatment. |
| 965 | 10230696 | We investigated whether cytokines produced primarily by monocytes/macrophages (IL-1alpha), Th1-lymphocytes (IFNgamma), or Th2-lymphocytes (IL-4) are modulated in diabetes-prone NOD mice by insulin treatment as used in prophylaxis studies. |
| 966 | 10230696 | IL-1alpha, IFNgamma and IL-4 were generally below detection in plasma of prediabetic animals and controls. |
| 967 | 10230696 | Supernatants of activated splenocytes from prediabetic NOD mice had lower levels of IL-4 (<15 pg/10(6) cells) compared with those from BALB/c mice (88+/-22 pg/10(6) cells; p<0.01), and this deficiency was partially compensated for when the NOD mice were given insulin (27+/-8; p<0.01). |
| 968 | 10230696 | The levels of IFNgamma were comparable and largely unaffected by insulin treatment. |
| 969 | 10230696 | We investigated whether cytokines produced primarily by monocytes/macrophages (IL-1alpha), Th1-lymphocytes (IFNgamma), or Th2-lymphocytes (IL-4) are modulated in diabetes-prone NOD mice by insulin treatment as used in prophylaxis studies. |
| 970 | 10230696 | IL-1alpha, IFNgamma and IL-4 were generally below detection in plasma of prediabetic animals and controls. |
| 971 | 10230696 | Supernatants of activated splenocytes from prediabetic NOD mice had lower levels of IL-4 (<15 pg/10(6) cells) compared with those from BALB/c mice (88+/-22 pg/10(6) cells; p<0.01), and this deficiency was partially compensated for when the NOD mice were given insulin (27+/-8; p<0.01). |
| 972 | 10230696 | The levels of IFNgamma were comparable and largely unaffected by insulin treatment. |
| 973 | 10330296 | Regulatory Th2-type T cell lines against insulin and GAD peptides derived from orally- and nasally-treated NOD mice suppress diabetes. |
| 974 | 10330296 | Ourselves and others have previously shown that oral and nasal administration of insulin or glutamic acid decarboxylase (GAD) suppresses development of diabetes in the NOD mouse and that this suppression appears secondary to the generation of regulatory T cells that act by secreting anti-inflammatory cytokines such as IL-4 and TGF-beta. |
| 975 | 10330296 | In the present study, we analysed cytokine patterns associated with mucosal administration of insulin B-chain, B-chain peptide 10-24 and GAD peptide 524-543 and derived lines and clones from mucosally-treated animals. |
| 976 | 10330296 | There was significantly less IFN-gamma production in mucosally-treated mice associated with increased production of IL-10 and TGF-beta. |
| 977 | 10330296 | T cell clones, established from draining lymph nodes of fed or nasally-treated animals, secreted IL-4, IL-10 and TGF-beta whereas those from non-fed mice secreted IL-2 and IFN-gamma. |
| 978 | 10330296 | Regulatory Th2-type T cell lines against insulin and GAD peptides derived from orally- and nasally-treated NOD mice suppress diabetes. |
| 979 | 10330296 | Ourselves and others have previously shown that oral and nasal administration of insulin or glutamic acid decarboxylase (GAD) suppresses development of diabetes in the NOD mouse and that this suppression appears secondary to the generation of regulatory T cells that act by secreting anti-inflammatory cytokines such as IL-4 and TGF-beta. |
| 980 | 10330296 | In the present study, we analysed cytokine patterns associated with mucosal administration of insulin B-chain, B-chain peptide 10-24 and GAD peptide 524-543 and derived lines and clones from mucosally-treated animals. |
| 981 | 10330296 | There was significantly less IFN-gamma production in mucosally-treated mice associated with increased production of IL-10 and TGF-beta. |
| 982 | 10330296 | T cell clones, established from draining lymph nodes of fed or nasally-treated animals, secreted IL-4, IL-10 and TGF-beta whereas those from non-fed mice secreted IL-2 and IFN-gamma. |
| 983 | 10330300 | GAD65 (glutamic acid decarboxylase) is an important autoantigen in both type 1 (insulin-dependent) diabetes mellitus (IDDM) and the neurological autoimmune disease stiff-man syndrome (SMS), and is expressed in pancreatic islets as well as the nervous system. |
| 984 | 10330300 | To study regulation of T cell responsiveness to GAD65, we investigated a non-diabetic SMS patient with HLA-DR3/7 (predisposing to type 1 diabetes) and high levels of type 1 diabetes-associated autoantibodies against GAD65 and islet cells, and compared the results with those of her diabetic son and two other SMS patients. |
| 985 | 10330300 | T cell responses to GAD65 were repeatedly absent in primary stimulation, whereas IA-2, islet antigen and tetanus toxoid induced significant T cell proliferation. |
| 986 | 10330300 | These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0). |
| 987 | 10337011 | Therefore, in order to evaluate cytokine secretion by spleen and islet infiltrating T cells in NOD mice at different stages of the autoimmune process, we developed an ELISPOT assay that detects IL-2, IL-4, and interferon-gamma (IFN-gamma) secretion in vitro at the single-cell level. |
| 988 | 10337011 | We showed that, whatever the age considered, IFN-gamma is predominantly secreted, and that no IL-4-secreting cells are detected in the islets of male and female NOD mice. |
| 989 | 10337011 | Spleen cells from 8-week-old female NOD mice, which include regulatory suppressor T cells, do not secrete IL-4, either upon presentation of islet cell antigens in vitro, or after transfer in vivo, but do secrete IFN-gamma. |
| 990 | 10337011 | IFN-gamma secretion by T cells from diabetic mice results from CD4 but not CD8 T cells in transfer experiments into NOD/severe combined immunodeficient (SCID) recipients. |
| 991 | 10337011 | These results suggest that (i) detection of regulatory CD4 T cells in NOD mice is not paralleled by a Th2 response; (ii) beta cell destruction does not depend on a switch from a Th2 to a Th1-type response; and (iii) CD8 T cells do not participate in induction of diabetes by secreting IFN-gamma. |
| 992 | 10337011 | Therefore, in order to evaluate cytokine secretion by spleen and islet infiltrating T cells in NOD mice at different stages of the autoimmune process, we developed an ELISPOT assay that detects IL-2, IL-4, and interferon-gamma (IFN-gamma) secretion in vitro at the single-cell level. |
| 993 | 10337011 | We showed that, whatever the age considered, IFN-gamma is predominantly secreted, and that no IL-4-secreting cells are detected in the islets of male and female NOD mice. |
| 994 | 10337011 | Spleen cells from 8-week-old female NOD mice, which include regulatory suppressor T cells, do not secrete IL-4, either upon presentation of islet cell antigens in vitro, or after transfer in vivo, but do secrete IFN-gamma. |
| 995 | 10337011 | IFN-gamma secretion by T cells from diabetic mice results from CD4 but not CD8 T cells in transfer experiments into NOD/severe combined immunodeficient (SCID) recipients. |
| 996 | 10337011 | These results suggest that (i) detection of regulatory CD4 T cells in NOD mice is not paralleled by a Th2 response; (ii) beta cell destruction does not depend on a switch from a Th2 to a Th1-type response; and (iii) CD8 T cells do not participate in induction of diabetes by secreting IFN-gamma. |
| 997 | 10337011 | Therefore, in order to evaluate cytokine secretion by spleen and islet infiltrating T cells in NOD mice at different stages of the autoimmune process, we developed an ELISPOT assay that detects IL-2, IL-4, and interferon-gamma (IFN-gamma) secretion in vitro at the single-cell level. |
| 998 | 10337011 | We showed that, whatever the age considered, IFN-gamma is predominantly secreted, and that no IL-4-secreting cells are detected in the islets of male and female NOD mice. |
| 999 | 10337011 | Spleen cells from 8-week-old female NOD mice, which include regulatory suppressor T cells, do not secrete IL-4, either upon presentation of islet cell antigens in vitro, or after transfer in vivo, but do secrete IFN-gamma. |
| 1000 | 10337011 | IFN-gamma secretion by T cells from diabetic mice results from CD4 but not CD8 T cells in transfer experiments into NOD/severe combined immunodeficient (SCID) recipients. |
| 1001 | 10337011 | These results suggest that (i) detection of regulatory CD4 T cells in NOD mice is not paralleled by a Th2 response; (ii) beta cell destruction does not depend on a switch from a Th2 to a Th1-type response; and (iii) CD8 T cells do not participate in induction of diabetes by secreting IFN-gamma. |
| 1002 | 10366128 | Association of interleukin-4 receptor and interleukin-4 promoter gene polymorphisms with systemic lupus erythematosus. |
| 1003 | 10400828 | Although we saw no difference in type 1 cytokine production (IL-2 and IFN-gamma) in either dialysis group, there was a clear increase in the percentage of T cells spontaneously producing the type 02 cytokines in the PD group (IL-4, r = 0.558, P < 0.05; IL-10, r = 0.527, p < 0.05). |
| 1004 | 10400828 | As expected there was no increase in the spontaneous production of either IL-4 or IL-10 in either disease group with patients undergoing HD treatment. |
| 1005 | 10400828 | However, there was a clear correlation with the frequency of T cells producing IL-4 (r = 0.755, P < 0.05) and IL-10 (r = 0.725, P < 0.05) and time on dialysis in the PD patients with DN, but not those with GN. |
| 1006 | 10400828 | Although we saw no difference in type 1 cytokine production (IL-2 and IFN-gamma) in either dialysis group, there was a clear increase in the percentage of T cells spontaneously producing the type 02 cytokines in the PD group (IL-4, r = 0.558, P < 0.05; IL-10, r = 0.527, p < 0.05). |
| 1007 | 10400828 | As expected there was no increase in the spontaneous production of either IL-4 or IL-10 in either disease group with patients undergoing HD treatment. |
| 1008 | 10400828 | However, there was a clear correlation with the frequency of T cells producing IL-4 (r = 0.755, P < 0.05) and IL-10 (r = 0.725, P < 0.05) and time on dialysis in the PD patients with DN, but not those with GN. |
| 1009 | 10400828 | Although we saw no difference in type 1 cytokine production (IL-2 and IFN-gamma) in either dialysis group, there was a clear increase in the percentage of T cells spontaneously producing the type 02 cytokines in the PD group (IL-4, r = 0.558, P < 0.05; IL-10, r = 0.527, p < 0.05). |
| 1010 | 10400828 | As expected there was no increase in the spontaneous production of either IL-4 or IL-10 in either disease group with patients undergoing HD treatment. |
| 1011 | 10400828 | However, there was a clear correlation with the frequency of T cells producing IL-4 (r = 0.755, P < 0.05) and IL-10 (r = 0.725, P < 0.05) and time on dialysis in the PD patients with DN, but not those with GN. |
| 1012 | 10404814 | Whereas no relation of PBMC reactivity with insulin autoantibodies was found, there was a positive correlation with the presence of at least one of the four autoantibodies tested and with IA-2 antibody. |
| 1013 | 10404814 | Furthermore, interleukin-4 (IL-4) production was lower in type 1 diabetic patients who proliferated to insulin than in those who did not (23+/-15 vs. 64+/-47 pg/mL; P = 0.04), but interferon-gamma, IL-2, and IL-10 productions were similar. |
| 1014 | 10411548 | Mice expressing lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) as a transgene in their beta cells develop insulin-dependent diabetes mellitus (IDDM) only after LCMV infection. |
| 1015 | 10411548 | Inoculation of plasmid DNA encoding the insulin B chain reduced the incidence of IDDM by 50% in this model. |
| 1016 | 10411548 | The insulin B-chain DNA vaccination was effective through induction of regulatory CD4 lymphocytes that react with the insulin B chain, secrete IL-4, and locally reduce activity of LCMV-NP-autoreactive cytotoxic T lymphocytes in the pancreatic draining lymph node. |
| 1017 | 10415012 | Peptide-based immunotherapy is one strategy by which to selectively suppress the T cell-mediated destruction of beta cells and treat insulin-dependent diabetes mellitus (IDDM). |
| 1018 | 10415012 | Here, we investigated whether a panel of T cell epitopes derived from the beta cell autoantigen glutamic acid decarboxylase 65 (GAD65) differ in their capacity to induce Th2 cell function in nonobese diabetic (NOD) mice and in turn prevent overt IDDM at different preclinical stages of disease development. |
| 1019 | 10415012 | Immunization with the GAD65-specific peptides did not block IDDM development in NOD mice deficient in IL-4 expression. |
| 1020 | 10415012 | These findings demonstrate that GAD65-specific peptide immunotherapy effectively suppresses progression to overt IDDM, requires the production of IL-4, and is dependent on the epitope targeted and the extent of preexisting beta cell autoimmunity in the recipient. |
| 1021 | 10415012 | Peptide-based immunotherapy is one strategy by which to selectively suppress the T cell-mediated destruction of beta cells and treat insulin-dependent diabetes mellitus (IDDM). |
| 1022 | 10415012 | Here, we investigated whether a panel of T cell epitopes derived from the beta cell autoantigen glutamic acid decarboxylase 65 (GAD65) differ in their capacity to induce Th2 cell function in nonobese diabetic (NOD) mice and in turn prevent overt IDDM at different preclinical stages of disease development. |
| 1023 | 10415012 | Immunization with the GAD65-specific peptides did not block IDDM development in NOD mice deficient in IL-4 expression. |
| 1024 | 10415012 | These findings demonstrate that GAD65-specific peptide immunotherapy effectively suppresses progression to overt IDDM, requires the production of IL-4, and is dependent on the epitope targeted and the extent of preexisting beta cell autoimmunity in the recipient. |
| 1025 | 10415077 | Interestingly, islet Ag-specific Th1 T cells were present and found to be functional, because neutralization of the Th2 effector cytokines IL-4 and IL-10 resulted in diabetes. |
| 1026 | 10415614 | Treatment of Balb/c male mice for two weeks resulted in the increase of IL-4, and the decrease of TNF-alpha, IFN-gamma, and IL-2 release from stimulated splenocytes, suggesting that UK-114 modulates the Th1/Th2 cytokine profile toward Th2. |
| 1027 | 10426368 | Accordingly, splenic lymphoid cells (SLC) from hIL-13-treated mice secreted less interferon (IFN)-gamma upon ex vivo stimulation with Concanavalin A than controls, and anti-CD3 monoclonal antibody-induced activation of T-cells in vivo resulted in lower blood levels of IFN-gamma and tumor necrosis factor-alpha and augmented blood levels of IL-4 in NOD mice pretreated with hIL-13. hIL-13 treatment also increased the blood levels of IgE and inhibited the transfer of type 1 diabetes by spleen cells from a diabetic donor to irradiated recipients. |
| 1028 | 10426368 | Taken together, these data add hIL-13 to the list of cytokines capable of downregulating immunoinflammatory diabetogenic pathways in NOD mice, and further support the concept that IL-4-related anti-inflammatory cytokines might have a role in the prevention of type 1 diabetes. |
| 1029 | 10426368 | Accordingly, splenic lymphoid cells (SLC) from hIL-13-treated mice secreted less interferon (IFN)-gamma upon ex vivo stimulation with Concanavalin A than controls, and anti-CD3 monoclonal antibody-induced activation of T-cells in vivo resulted in lower blood levels of IFN-gamma and tumor necrosis factor-alpha and augmented blood levels of IL-4 in NOD mice pretreated with hIL-13. hIL-13 treatment also increased the blood levels of IgE and inhibited the transfer of type 1 diabetes by spleen cells from a diabetic donor to irradiated recipients. |
| 1030 | 10426368 | Taken together, these data add hIL-13 to the list of cytokines capable of downregulating immunoinflammatory diabetogenic pathways in NOD mice, and further support the concept that IL-4-related anti-inflammatory cytokines might have a role in the prevention of type 1 diabetes. |
| 1031 | 10433100 | By analysis of cytokine RNA production we found that treatment of several strains of mice with streptozotocin changes the peripheral helper T cell phenotype elicited after immunization with Keyhole Limpet Hemocyanin from a mixed Th1- and Th2-type cytokine pattern (characterized by IFN-gamma and IL-4 and IL-5 expressions, respectively) to predominately Th1-type. |
| 1032 | 10435719 | Failure of exogenously administered interferon-gamma or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice. |
| 1033 | 10435719 | Interferon (IFN)-gamma and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. |
| 1034 | 10435719 | The capacity of male NOD mice to produce more IL-4 and less IFN-gamma within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. |
| 1035 | 10435719 | In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-gamma, mouse IFN-gamma, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. |
| 1036 | 10435719 | Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-gamma or specific IL-4 inhibitors. |
| 1037 | 10435719 | These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-gamma or IL-4. |
| 1038 | 10435719 | Failure of exogenously administered interferon-gamma or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice. |
| 1039 | 10435719 | Interferon (IFN)-gamma and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. |
| 1040 | 10435719 | The capacity of male NOD mice to produce more IL-4 and less IFN-gamma within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. |
| 1041 | 10435719 | In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-gamma, mouse IFN-gamma, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. |
| 1042 | 10435719 | Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-gamma or specific IL-4 inhibitors. |
| 1043 | 10435719 | These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-gamma or IL-4. |
| 1044 | 10435719 | Failure of exogenously administered interferon-gamma or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice. |
| 1045 | 10435719 | Interferon (IFN)-gamma and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. |
| 1046 | 10435719 | The capacity of male NOD mice to produce more IL-4 and less IFN-gamma within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. |
| 1047 | 10435719 | In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-gamma, mouse IFN-gamma, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. |
| 1048 | 10435719 | Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-gamma or specific IL-4 inhibitors. |
| 1049 | 10435719 | These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-gamma or IL-4. |
| 1050 | 10435719 | Failure of exogenously administered interferon-gamma or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice. |
| 1051 | 10435719 | Interferon (IFN)-gamma and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. |
| 1052 | 10435719 | The capacity of male NOD mice to produce more IL-4 and less IFN-gamma within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. |
| 1053 | 10435719 | In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-gamma, mouse IFN-gamma, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. |
| 1054 | 10435719 | Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-gamma or specific IL-4 inhibitors. |
| 1055 | 10435719 | These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-gamma or IL-4. |
| 1056 | 10435719 | Failure of exogenously administered interferon-gamma or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice. |
| 1057 | 10435719 | Interferon (IFN)-gamma and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. |
| 1058 | 10435719 | The capacity of male NOD mice to produce more IL-4 and less IFN-gamma within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. |
| 1059 | 10435719 | In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-gamma, mouse IFN-gamma, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. |
| 1060 | 10435719 | Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-gamma or specific IL-4 inhibitors. |
| 1061 | 10435719 | These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-gamma or IL-4. |
| 1062 | 10435719 | Failure of exogenously administered interferon-gamma or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice. |
| 1063 | 10435719 | Interferon (IFN)-gamma and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. |
| 1064 | 10435719 | The capacity of male NOD mice to produce more IL-4 and less IFN-gamma within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. |
| 1065 | 10435719 | In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-gamma, mouse IFN-gamma, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. |
| 1066 | 10435719 | Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-gamma or specific IL-4 inhibitors. |
| 1067 | 10435719 | These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-gamma or IL-4. |
| 1068 | 10438916 | In the latter model transgenic mice express the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promotor (RIP) in the pancreatic beta cells and develop diabetes only following LCMV infection; and 2) protection could be transferred with insulin B chain-restimulated but not LCMV-restimulated splenocytes from RIP-NP transgenic mice, demonstrating that the mechanism of diabetes prevention in the RIP-NP model is mediated by insulin B chain-specific, IL-4-producing regulatory cells acting as bystander suppressors. |
| 1069 | 10449167 | Our work has been concerned with the detailed characterization of four distinct DC populations in NOD mice: two derived from bone marrow (BM) cells cultured in either granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4) or GM-CSF alone and two from the spleen of Flt3 ligand (Flt3L) -treated mice, isolated on the basis of CD8alpha expression. |
| 1070 | 10449167 | In addition, we obtained a lower yield of NOD BM-derived DC and they expressed higher levels of cell-surface CD40 and IL-12 p40 mRNA than BM-derived DC from the diabetes-resistant strain, B10.BR. |
| 1071 | 10450506 | These animals were also deficient in the rapid production of interleukin-4 and interferon-gamma in response to stimulation by anti-CD3 antibodies. |
| 1072 | 10453045 | IL-12 and IL-12 antagonist administration to nonobese diabetic (NOD) mice accelerates and prevents insulin-dependent diabetes mellitus (IDDM), respectively. |
| 1073 | 10453045 | Nevertheless, wild-type and IL-12-deficient NOD mice developed similar insulitis and IDDM. |
| 1074 | 10453045 | Both in wild-type and IL-12-deficient NOD mice, approximately 20% of pancreas-infiltrating CD4+ T cells produced IFN-gamma, whereas very few produced IL-10 or IL-4, indicating that IDDM was associated with a type 1 T cell infiltrate in the target organ. |
| 1075 | 10455925 | IL-4 production in IDDM-nonrecurrent pancreas-transplanted BB rats with donor-derived NKR-P1+TCR alpha beta + (NKT) cells, but not in IDDM-recurrent BB rats. |
| 1076 | 10464178 | Furthermore, NOD mice which spontaneously develop diabetes are susceptible to EAE induction with myelin oligodendrocyte glycoprotein (MOG) 35-55, whereas a MHC congenic strain, III, which also expresses I-A(g7) MHC haplotype does not develop diabetes and is also resistant to EAE induction. |
| 1077 | 10464178 | In the susceptible strains (SJL and NOD) in vitro, there are high levels of IFN-gamma production, whereas the resistant strains (B10.S or III) secreted primarily IL-4/IL-10 and transforming growth factor (TGF)-beta, and had decreased levels of IFN-gamma. |
| 1078 | 10464178 | When brains from susceptible and resistant mice were examined by immunohistochemical methods for cytokine expression, the brains from resistant mice showed fewer infiltrates which predominantly expressed IL-4 and IL-10 and/or TGF-beta. |
| 1079 | 10464178 | Brains from NOD and SJL with EAE showed mainly IL-2 and IFN-gamma positive cells. |
| 1080 | 10464178 | Furthermore, NOD mice which spontaneously develop diabetes are susceptible to EAE induction with myelin oligodendrocyte glycoprotein (MOG) 35-55, whereas a MHC congenic strain, III, which also expresses I-A(g7) MHC haplotype does not develop diabetes and is also resistant to EAE induction. |
| 1081 | 10464178 | In the susceptible strains (SJL and NOD) in vitro, there are high levels of IFN-gamma production, whereas the resistant strains (B10.S or III) secreted primarily IL-4/IL-10 and transforming growth factor (TGF)-beta, and had decreased levels of IFN-gamma. |
| 1082 | 10464178 | When brains from susceptible and resistant mice were examined by immunohistochemical methods for cytokine expression, the brains from resistant mice showed fewer infiltrates which predominantly expressed IL-4 and IL-10 and/or TGF-beta. |
| 1083 | 10464178 | Brains from NOD and SJL with EAE showed mainly IL-2 and IFN-gamma positive cells. |
| 1084 | 10512358 | In a number of animal models of spontaneous autoimmune diabetes, pathogenesis has been highly correlated with autoreactive T-cell production of the type 1 cytokine interferon-gamma (IFN-gamma), while protection from disease was associated with type 2 cytokines such as interleukin (IL)-4. |
| 1085 | 10512358 | IL-10 has generally been associated with immunosuppression, including the modulation of class II expression on antigen-presenting cells and the generation of regulatory CD4 T-cells. |
| 1086 | 10525315 | We have constructed bone marrow chimeras between transgenic and non-transgenic NOD mice to study the correlation of E expression on bone marrow derived cells and thymic epithelium vs the production of IL-4 and IFN-gamma. |
| 1087 | 10549628 | Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/Stat6 pathway. |
| 1088 | 10549628 | Here, we report the generation and characterization of insulin B chain-specific "autoreactive" CD4+ regulatory T cells that locally suppress diabetogenic T cell responses against an unrelated self-antigen (viral transgene) in a virus-induced model for type 1 diabetes. |
| 1089 | 10576558 | In contrast, IFNgamma production was not affected while IL-10 levels were slightly decreased. |
| 1090 | 10576558 | The differential effect of the NO donor on IL-4 versus IL-10 and IFNgamma gene expression suggests an immunomodulatory potential of NO, which may serve to limit inflammatory responses. |
| 1091 | 10580417 | DCs derived from GM-CSF [granulocyte/macrophage colony-stimulating factor] + interleukin (IL)-4 cultures expressed high levels of major histocompatibility complex (MHC) class II, CD40, CD80, and CD86 molecules and were efficient stimulators of naive allogeneic T-cells. |
| 1092 | 10580417 | In contrast, DCs derived from GM-CSF cultures had low levels of MHC class II costimulation/activation molecules, were able to take up mannosylated bovine serum albumin more efficiently than GM + IL-4 DCs, and were poor T-cell stimulators. |
| 1093 | 10580417 | DCs derived from GM-CSF [granulocyte/macrophage colony-stimulating factor] + interleukin (IL)-4 cultures expressed high levels of major histocompatibility complex (MHC) class II, CD40, CD80, and CD86 molecules and were efficient stimulators of naive allogeneic T-cells. |
| 1094 | 10580417 | In contrast, DCs derived from GM-CSF cultures had low levels of MHC class II costimulation/activation molecules, were able to take up mannosylated bovine serum albumin more efficiently than GM + IL-4 DCs, and were poor T-cell stimulators. |
| 1095 | 10585754 | It has been suggested that in cell-mediated autoimmune diseases, Th2-like lymphocytes secreting IL-4 and/or IL-10 provide protection, while Th1-like cells secreting IFN-gamma are pathogenic. |
| 1096 | 10585754 | We provide here evidence that IFN-gamma producers are relatively resistant to depletion by CY and that Th0 clones can be shifted towards Th1. |
| 1097 | 10585754 | Thus, the acceleration of diabetes by CY seems to be a complex event, which includes the relatively high resistance of IFN-gamma producers to the drug, their rapid reconstitution, and a Th1 shift of surviving T cell clones. |
| 1098 | 10605017 | We now demonstrate that regulatory splenocytes belong to the CD4+ CD62Lhigh T cell subset that comprises a vast majority of naive cells producing low levels of IL-2 and IFN-gamma and no IL-4 and IL-10 upon in vitro stimulation. |
| 1099 | 10605017 | Consistently, the inhibition of diabetes transfer was not mediated by IL-4 and IL-10. |
| 1100 | 10605017 | The phenotypic and functional characteristics of protective CD4+ CD62L+ cells suggest they are different from Th2-, Tr1-, and NK T-type cells, reported to be implicated in the control of diabetes in NOD mice, and may represent a new immunoregulatory population. |
| 1101 | 10605017 | We now demonstrate that regulatory splenocytes belong to the CD4+ CD62Lhigh T cell subset that comprises a vast majority of naive cells producing low levels of IL-2 and IFN-gamma and no IL-4 and IL-10 upon in vitro stimulation. |
| 1102 | 10605017 | Consistently, the inhibition of diabetes transfer was not mediated by IL-4 and IL-10. |
| 1103 | 10605017 | The phenotypic and functional characteristics of protective CD4+ CD62L+ cells suggest they are different from Th2-, Tr1-, and NK T-type cells, reported to be implicated in the control of diabetes in NOD mice, and may represent a new immunoregulatory population. |
| 1104 | 10620608 | The diabetes was accompanied by severe insulitis composed of both T cells (CD4(+) and CD8(+)) and B cells. |
| 1105 | 10620608 | T cells from the diabetic mice secreted large amounts of interferon gamma, but not interleukin 4, in response to DQ8(+) islets and the putative islet autoantigens, insulin and glutamic acid decarboxylase (GAD). |
| 1106 | 10620608 | In conclusion, substitution of HLA-DQA1*0301/DQB1*0302, but not HLA-DQA1*0103/DQB1*0601, for murine MHC class II provokes autoimmune diabetes in non-diabetes-prone rat insulin promoter (RIP).B7-1 C57BL/6 mice. |
| 1107 | 10674354 | IL4 and IL4Ralpha genes are not linked or associated with type 1 diabetes. |
| 1108 | 10674354 | Here we have evaluated IL4 and the alpha subunit of the IL-4 receptor (IL4Ralpha) genes using the affected sibpair (ASP) and transmission/disequilibrium test (TDT). |
| 1109 | 10674354 | IL4 and IL4Ralpha genes are not linked or associated with type 1 diabetes. |
| 1110 | 10674354 | Here we have evaluated IL4 and the alpha subunit of the IL-4 receptor (IL4Ralpha) genes using the affected sibpair (ASP) and transmission/disequilibrium test (TDT). |
| 1111 | 10689643 | Th1 (IFN-gamma and TNF-beta) and Th2 (IL-4 and IL-10) cytokine mRNA expression was analyzed in pancreatic islets isolated from female NOD mice with a high incidence of diabetes and male NOD mice with a low incidence of diabetes. |
| 1112 | 10689643 | These results suggest that islet beta-cell destruction and diabetes in female NOD mice correlates with IFN-gamma and TNF-beta production in the islets, and that male NOD mice may be protected from autoimmune beta-cell destruction by down-regulation of these cytokines. |
| 1113 | 10689643 | Furthermore, our findings also suggest that insulitis and beta-cell destruction are independently regulated: TNF-beta is more important in forming and maintaining the insulitis, while IFN-gamma has a more important role in beta-cell destruction. |
| 1114 | 10707936 | Neither the pancreata of normal BALB/c mice nor NOD mice at 2-16 weeks of age contained tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), IL-4, or IL-12. |
| 1115 | 10707936 | At 8 weeks of age, a few IL-2+ cells were found in the pancreas of one of three NOD mice. |
| 1116 | 10707937 | Sections from the pancreata of these injected mice were stained for cytokines (tumor necrosis factor alpha [TNF-alpha], interferon gamma [IFN-gamma], CD1d, interleukin 2 [IL-2], IL-4, IL-6, IL-10, and IL-12). |
| 1117 | 10707937 | The expression of IL-2 and IL-12 was very scarce. |
| 1118 | 10714554 | The aim of this study was to investigate the frequency of a CA dinucleotide repeat polymorphism in the interferon-gamma (IFN-gamma) gene (IFNG) and a C(-590)T polymorphism of the interleukin-4 (IL-4) gene in 236 Caucasoid patients with type 1 diabetes. |
| 1119 | 10725719 | Anti-LFA-1 therapy induces long-term islet allograft acceptance in the absence of IFN-gamma or IL-4. |
| 1120 | 10725719 | Finally, anti-LFA-1 treatment was effective in both IL-4-deficient and IFN-gamma-deficient recipients, indicating that neither of these cytokines are universally required for allograft acceptance. |
| 1121 | 10725719 | These results suggest that anti-adhesion-based therapy can induce a nondeletional form of tolerance that is not overtly dependent on the prototypic Th1 and Th2 cytokines, IFN-gamma and IL-4, respectively, in contrast to results in other transplantation models. |
| 1122 | 10725719 | Anti-LFA-1 therapy induces long-term islet allograft acceptance in the absence of IFN-gamma or IL-4. |
| 1123 | 10725719 | Finally, anti-LFA-1 treatment was effective in both IL-4-deficient and IFN-gamma-deficient recipients, indicating that neither of these cytokines are universally required for allograft acceptance. |
| 1124 | 10725719 | These results suggest that anti-adhesion-based therapy can induce a nondeletional form of tolerance that is not overtly dependent on the prototypic Th1 and Th2 cytokines, IFN-gamma and IL-4, respectively, in contrast to results in other transplantation models. |
| 1125 | 10725719 | Anti-LFA-1 therapy induces long-term islet allograft acceptance in the absence of IFN-gamma or IL-4. |
| 1126 | 10725719 | Finally, anti-LFA-1 treatment was effective in both IL-4-deficient and IFN-gamma-deficient recipients, indicating that neither of these cytokines are universally required for allograft acceptance. |
| 1127 | 10725719 | These results suggest that anti-adhesion-based therapy can induce a nondeletional form of tolerance that is not overtly dependent on the prototypic Th1 and Th2 cytokines, IFN-gamma and IL-4, respectively, in contrast to results in other transplantation models. |
| 1128 | 10741564 | An islet-specific CD8+ T cell hybridoma generated from non-obese diabetic mice recognizes insulin as an autoantigen. |
| 1129 | 10741564 | Although CD8+ T cells play a major role in beta cell destruction in insulin-dependent diabetes in the non-obese diabetic mouse, the T cell autoantigen(s) recognized by such cells remains to be identified. |
| 1130 | 10741564 | In the presence of islets, none of the 12 CD3+ CD8+ T cell hybridomas isolated secreted IL-2/IL-4 or IFNgamma but three were islet specific, as shown by activation induced cell death. |
| 1131 | 10741569 | The ABBOS-peptide from bovine serum albumin causes an IFN-gamma and IL-4 mRNA response in lymphocytes from children with recent onset of type 1 diabetes. |
| 1132 | 10741569 | The cytokines IL-4 and IFN-gamma were determined at the level of transcription as mRNA in lymphocytes, stimulated with the ABBOS-peptide. |
| 1133 | 10741569 | Antibodies to bovine serum albumin (BSA), insulin antibodies (IA), and antibodies against islet cells (ICA) were determined, as well as serum C-peptide. |
| 1134 | 10741569 | Increased mRNA expression for IFN-gamma and/or IL-4 could be observed in lymphocytes from 13/16 children with recent onset of diabetes after in vitro stimulation with the ABBOS-peptide. |
| 1135 | 10741569 | Low expression of IFN-gamma mRNA was associated with high secretion of C-peptide, whereas a positive relationship could be observed between expression of IL-4 mRNA and insulin antibodies. |
| 1136 | 10741569 | Expression of IFN-gamma and/or IL-4 mRNA was also detected in lymphocytes from 6/10 healthy controls. |
| 1137 | 10741569 | The ABBOS-peptide from bovine serum albumin causes an IFN-gamma and IL-4 mRNA response in lymphocytes from children with recent onset of type 1 diabetes. |
| 1138 | 10741569 | The cytokines IL-4 and IFN-gamma were determined at the level of transcription as mRNA in lymphocytes, stimulated with the ABBOS-peptide. |
| 1139 | 10741569 | Antibodies to bovine serum albumin (BSA), insulin antibodies (IA), and antibodies against islet cells (ICA) were determined, as well as serum C-peptide. |
| 1140 | 10741569 | Increased mRNA expression for IFN-gamma and/or IL-4 could be observed in lymphocytes from 13/16 children with recent onset of diabetes after in vitro stimulation with the ABBOS-peptide. |
| 1141 | 10741569 | Low expression of IFN-gamma mRNA was associated with high secretion of C-peptide, whereas a positive relationship could be observed between expression of IL-4 mRNA and insulin antibodies. |
| 1142 | 10741569 | Expression of IFN-gamma and/or IL-4 mRNA was also detected in lymphocytes from 6/10 healthy controls. |
| 1143 | 10741569 | The ABBOS-peptide from bovine serum albumin causes an IFN-gamma and IL-4 mRNA response in lymphocytes from children with recent onset of type 1 diabetes. |
| 1144 | 10741569 | The cytokines IL-4 and IFN-gamma were determined at the level of transcription as mRNA in lymphocytes, stimulated with the ABBOS-peptide. |
| 1145 | 10741569 | Antibodies to bovine serum albumin (BSA), insulin antibodies (IA), and antibodies against islet cells (ICA) were determined, as well as serum C-peptide. |
| 1146 | 10741569 | Increased mRNA expression for IFN-gamma and/or IL-4 could be observed in lymphocytes from 13/16 children with recent onset of diabetes after in vitro stimulation with the ABBOS-peptide. |
| 1147 | 10741569 | Low expression of IFN-gamma mRNA was associated with high secretion of C-peptide, whereas a positive relationship could be observed between expression of IL-4 mRNA and insulin antibodies. |
| 1148 | 10741569 | Expression of IFN-gamma and/or IL-4 mRNA was also detected in lymphocytes from 6/10 healthy controls. |
| 1149 | 10741569 | The ABBOS-peptide from bovine serum albumin causes an IFN-gamma and IL-4 mRNA response in lymphocytes from children with recent onset of type 1 diabetes. |
| 1150 | 10741569 | The cytokines IL-4 and IFN-gamma were determined at the level of transcription as mRNA in lymphocytes, stimulated with the ABBOS-peptide. |
| 1151 | 10741569 | Antibodies to bovine serum albumin (BSA), insulin antibodies (IA), and antibodies against islet cells (ICA) were determined, as well as serum C-peptide. |
| 1152 | 10741569 | Increased mRNA expression for IFN-gamma and/or IL-4 could be observed in lymphocytes from 13/16 children with recent onset of diabetes after in vitro stimulation with the ABBOS-peptide. |
| 1153 | 10741569 | Low expression of IFN-gamma mRNA was associated with high secretion of C-peptide, whereas a positive relationship could be observed between expression of IL-4 mRNA and insulin antibodies. |
| 1154 | 10741569 | Expression of IFN-gamma and/or IL-4 mRNA was also detected in lymphocytes from 6/10 healthy controls. |
| 1155 | 10741569 | The ABBOS-peptide from bovine serum albumin causes an IFN-gamma and IL-4 mRNA response in lymphocytes from children with recent onset of type 1 diabetes. |
| 1156 | 10741569 | The cytokines IL-4 and IFN-gamma were determined at the level of transcription as mRNA in lymphocytes, stimulated with the ABBOS-peptide. |
| 1157 | 10741569 | Antibodies to bovine serum albumin (BSA), insulin antibodies (IA), and antibodies against islet cells (ICA) were determined, as well as serum C-peptide. |
| 1158 | 10741569 | Increased mRNA expression for IFN-gamma and/or IL-4 could be observed in lymphocytes from 13/16 children with recent onset of diabetes after in vitro stimulation with the ABBOS-peptide. |
| 1159 | 10741569 | Low expression of IFN-gamma mRNA was associated with high secretion of C-peptide, whereas a positive relationship could be observed between expression of IL-4 mRNA and insulin antibodies. |
| 1160 | 10741569 | Expression of IFN-gamma and/or IL-4 mRNA was also detected in lymphocytes from 6/10 healthy controls. |
| 1161 | 10746656 | Thus, supernatants of islets from these mice contained increased levels of interleukin (IL)-4, IL-10, and, to a lesser extent, interferon-gamma and diminished levels of tumor necrosis factor-a compared with controls. |
| 1162 | 10746656 | Because exogenous IL-4 and IL-10 exert antidiabetogenic effect in NOD mice and early blockade of endogenous tumor necrosis factor-alpha prevents NOD mouse diabetes, these phenomena may be causally related to the antidiabetogenic effect of HGG-pulsed DC treatment. |
| 1163 | 10746656 | Thus, supernatants of islets from these mice contained increased levels of interleukin (IL)-4, IL-10, and, to a lesser extent, interferon-gamma and diminished levels of tumor necrosis factor-a compared with controls. |
| 1164 | 10746656 | Because exogenous IL-4 and IL-10 exert antidiabetogenic effect in NOD mice and early blockade of endogenous tumor necrosis factor-alpha prevents NOD mouse diabetes, these phenomena may be causally related to the antidiabetogenic effect of HGG-pulsed DC treatment. |
| 1165 | 10753067 | Intramuscular administration of expression plasmids encoding interferon-gamma receptor/IgG1 or IL-4/IgG1 chimeric proteins protects from autoimmunity. |
| 1166 | 10770268 | One of the primary mechanisms of active cellular suppression is via secretion of suppressive cytokines such as TGF-beta, IL-4, and IL-10 following antigen-specific triggering. |
| 1167 | 10770268 | TGF-beta is produced both by CD4+ and CD8+ GALT-derived T cells and is an important mediator of the active suppression component of oral tolerance. |
| 1168 | 10773364 | The popliteal lymph node response to streptozotocin is under type 1, MHC class-I restricted, CD8(+) T-cell control. |
| 1169 | 10773364 | In order to determine whether PLN responses involve CD4(+) or CD8(+) T-cells, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analyzed after injection into the hind footpad of C57 BL/6 mice and major histocompatibility complex (MHC) class I or II deficient mice. |
| 1170 | 10773364 | The involvement of type 1 or type 2 cell control on the production of cytokine mRNAs was analyzed in lymph node cells by quantitative RT-PCR, together with the analysis of a wide range of cytokine mRNAs after STZ injection (IL-1alpha, IL-1beta, TNF-alpha, IFN-gamma, IL-2, IL-2 receptor, IL-4, IL-5, IL-6, IL-10 and IL-12). |
| 1171 | 10773364 | We have found that mice depleted in CD8(+) T-cells did not respond to STZ, whereas mice depleted in CD4(+) T-cells exhibited the expected positive PLN responses, with increased weight and cellularity indices. |
| 1172 | 10773364 | STZ induced a low production of interleukin (IL)-2 mRNAs, a mild increase in IL-1alpha and IL-6 mRNAs production, and a dramatic increase in IFN-gamma, IL-1beta, TNF-alpha, IL-12 and IL-2 receptor mRNAs, which correlated with positive PLN responses. |
| 1173 | 10773364 | No effects on IL-4, IL-5 and IL-10 mRNAs synthesis were noted. |
| 1174 | 10773364 | In CD8(+) T-cell deficient mice, there was no production of IFN-gamma or IL-6 mRNAs. |
| 1175 | 10773364 | These results suggest that PLN responses to STZ are under the control of type 1, MHC class-I-restricted, CD8(+) T-cells. |
| 1176 | 10773364 | The popliteal lymph node response to streptozotocin is under type 1, MHC class-I restricted, CD8(+) T-cell control. |
| 1177 | 10773364 | In order to determine whether PLN responses involve CD4(+) or CD8(+) T-cells, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analyzed after injection into the hind footpad of C57 BL/6 mice and major histocompatibility complex (MHC) class I or II deficient mice. |
| 1178 | 10773364 | The involvement of type 1 or type 2 cell control on the production of cytokine mRNAs was analyzed in lymph node cells by quantitative RT-PCR, together with the analysis of a wide range of cytokine mRNAs after STZ injection (IL-1alpha, IL-1beta, TNF-alpha, IFN-gamma, IL-2, IL-2 receptor, IL-4, IL-5, IL-6, IL-10 and IL-12). |
| 1179 | 10773364 | We have found that mice depleted in CD8(+) T-cells did not respond to STZ, whereas mice depleted in CD4(+) T-cells exhibited the expected positive PLN responses, with increased weight and cellularity indices. |
| 1180 | 10773364 | STZ induced a low production of interleukin (IL)-2 mRNAs, a mild increase in IL-1alpha and IL-6 mRNAs production, and a dramatic increase in IFN-gamma, IL-1beta, TNF-alpha, IL-12 and IL-2 receptor mRNAs, which correlated with positive PLN responses. |
| 1181 | 10773364 | No effects on IL-4, IL-5 and IL-10 mRNAs synthesis were noted. |
| 1182 | 10773364 | In CD8(+) T-cell deficient mice, there was no production of IFN-gamma or IL-6 mRNAs. |
| 1183 | 10773364 | These results suggest that PLN responses to STZ are under the control of type 1, MHC class-I-restricted, CD8(+) T-cells. |
| 1184 | 10797469 | Increased production of interferon-gamma, but not IL-4 mRNA, by streptozotocin in the popliteal lymph node assay. |
| 1185 | 10797469 | To determine whether PLN responses involved Th1 or Th2 cell control, or both, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analysed on the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA by lymph node cells after injection into the hind footpad of C57 BL/6 mice. |
| 1186 | 10797469 | Increased production of interferon-gamma, but not IL-4 mRNA, by streptozotocin in the popliteal lymph node assay. |
| 1187 | 10797469 | To determine whether PLN responses involved Th1 or Th2 cell control, or both, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analysed on the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA by lymph node cells after injection into the hind footpad of C57 BL/6 mice. |
| 1188 | 10814778 | Hsp60 expression was found to be enhanced in response to cytokines as diverse as IL-1beta, TNF-alpha, IL-4, IL-6 and IL-10. |
| 1189 | 10814778 | Upregulation of hsp27, however, was primarily induced by immunoregulatory cytokines like IL-4, IL-6 and TGF-beta whereas alphaB-crystallin expression was found to be enhanced by the pro-inflammatory cytokine TNF-alpha only. |
| 1190 | 10814778 | Hsp60 expression was found to be enhanced in response to cytokines as diverse as IL-1beta, TNF-alpha, IL-4, IL-6 and IL-10. |
| 1191 | 10814778 | Upregulation of hsp27, however, was primarily induced by immunoregulatory cytokines like IL-4, IL-6 and TGF-beta whereas alphaB-crystallin expression was found to be enhanced by the pro-inflammatory cytokine TNF-alpha only. |
| 1192 | 10832976 | IFN-gamma production from splenic T lymphocytes stimulated with anti-CD3 monoclonal antibodies was increased, whereas IL-4 production was decreased in NOD controls compared to age- and sex-matched normal ICR mice. |
| 1193 | 10843746 | Production of IL-10 and IL-12 in CD40 and interleukin 4-activated mononuclear cells from patients with Graves' disease. |
| 1194 | 10843746 | We investigated the effect of T cell-dependent B cell activation on the production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) obtained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. |
| 1195 | 10843746 | In subjects with a low basal IL-12 level there was a positive correlation between the production of IL-12 and that of IL-10 from PBMCs stimulated with anti-CD40 antibodies plus IL-4. |
| 1196 | 10843746 | Thus, T cell-dependent B cell activation via a CD40 pathway triggers the overproduction of IL-10 and overcome the effect of IL-12 to shift the Th(1)/Th(2)balance to Th(2)dominance in patients with Graves' disease but not in Hashimoto's thyroiditis or type 1 diabetes. |
| 1197 | 10843746 | Production of IL-10 and IL-12 in CD40 and interleukin 4-activated mononuclear cells from patients with Graves' disease. |
| 1198 | 10843746 | We investigated the effect of T cell-dependent B cell activation on the production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) obtained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. |
| 1199 | 10843746 | In subjects with a low basal IL-12 level there was a positive correlation between the production of IL-12 and that of IL-10 from PBMCs stimulated with anti-CD40 antibodies plus IL-4. |
| 1200 | 10843746 | Thus, T cell-dependent B cell activation via a CD40 pathway triggers the overproduction of IL-10 and overcome the effect of IL-12 to shift the Th(1)/Th(2)balance to Th(2)dominance in patients with Graves' disease but not in Hashimoto's thyroiditis or type 1 diabetes. |
| 1201 | 10872884 | Temporal relationship between immune cell influx and the expression of inducible nitric oxide synthase, interleukin-4 and interferon-gamma in pancreatic islets of NOD mice following adoptive transfer of diabetic spleen cells. |
| 1202 | 10872884 | The progression of insulitis and the number of intra-islet CD4 and CD8 cells and macrophages were correlated with the expression and co-localization of inducible nitric oxide synthase, interferon-gamma and interleukin-4 by dual-label light and confocal immunofluorescence microscopy. |
| 1203 | 10872884 | During the period of heightened insulitis, selective immune cells begin to express inducible nitric oxide synthase and the opposing cytokines, interferon-gamma and interleukin-4. |
| 1204 | 10872884 | Temporal relationship between immune cell influx and the expression of inducible nitric oxide synthase, interleukin-4 and interferon-gamma in pancreatic islets of NOD mice following adoptive transfer of diabetic spleen cells. |
| 1205 | 10872884 | The progression of insulitis and the number of intra-islet CD4 and CD8 cells and macrophages were correlated with the expression and co-localization of inducible nitric oxide synthase, interferon-gamma and interleukin-4 by dual-label light and confocal immunofluorescence microscopy. |
| 1206 | 10872884 | During the period of heightened insulitis, selective immune cells begin to express inducible nitric oxide synthase and the opposing cytokines, interferon-gamma and interleukin-4. |
| 1207 | 10872884 | Temporal relationship between immune cell influx and the expression of inducible nitric oxide synthase, interleukin-4 and interferon-gamma in pancreatic islets of NOD mice following adoptive transfer of diabetic spleen cells. |
| 1208 | 10872884 | The progression of insulitis and the number of intra-islet CD4 and CD8 cells and macrophages were correlated with the expression and co-localization of inducible nitric oxide synthase, interferon-gamma and interleukin-4 by dual-label light and confocal immunofluorescence microscopy. |
| 1209 | 10872884 | During the period of heightened insulitis, selective immune cells begin to express inducible nitric oxide synthase and the opposing cytokines, interferon-gamma and interleukin-4. |
| 1210 | 10878389 | Whereas an elevated ratio of macrophage inflammatory protein-1alpha (MIP-1alpha):MIP-1beta in the pancreas correlated with destructive insulitis and progression to diabetes in NOD mice, a decreased intrapancreatic MIP-1alpha:MIP-1beta ratio was observed in nonobese diabetes-resistant (NOR) mice. |
| 1211 | 10878389 | IL-4 treatment, which prevents diabetes in NOD mice by polarizing intraislet Th2 responses, decreased CCR5 expression in islets and potentiated a high ratio of MIP-1beta and monocyte chemotactic protein-1 (MCP-1): MIP-1alpha in the pancreas. |
| 1212 | 10878389 | These studies illustrate that the temporal expression of certain CC chemokines, particularly MIP-1alpha, and the CCR5 chemokine receptor in the pancreas is associated with the development of insulitis and spontaneous type I diabetes. |
| 1213 | 10936088 | However, in additional cases T-cell responses to P2C were detectable through the release of interferon-gamma or interleukin-4 in individuals who did not make proliferative responses. |
| 1214 | 10953913 | Genes encoding transforming growth factor beta, interleukin-4 (IL-4) and IL-10 are most frequently protective. |
| 1215 | 10953913 | Autoimmune/ inflammatory diseases are associated with excessive production of inflammatory cytokines such as IL-1, IL-12, tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma). |
| 1216 | 10953913 | Vectors encoding inhibitors of these cytokines, such as IL-1 receptor antagonist, soluble IL-1 receptors, IL-12p40, soluble TNFalpha receptors or IFNgamma-receptor/IgG-Fc fusion proteins are protective in models of either arthritis, Type 1 DM, SLE or EAE. |
| 1217 | 10975477 | Intracellular cytokine staining and flow cytometry were used to investigate whether immunoadsorption (IA) of immunoglobulins alters intracytoplasmic cytokine production in CD4+ and CD8+ T cells from the blood of patients with refractory rheumatoid arthritis (n = 7), membrane proliferative glomerulonephritis (n = 1), and Goodpasture's syndrome (n = 1). |
| 1218 | 10975477 | Four patients (Group 1) showed severely depressed production of TNF-alpha, IL-2, IFN-gamma, and IL-4 by CD4+ and CD8+ T cells and responded to 3 IA sessions with significant increases in CD4+TNF-alpha+, CD4+IL-2+, and CD8+IL-2+ T cells. |
| 1219 | 10975477 | Also, a tendency toward increased percentage levels of CD4+ T cells producing IFN-gamma or IL-4 and of CD8+ T cells producing either TNF-alpha or IFN-gamma was seen, but due to the small number of patients investigated, these differences did not attain statistic significance. |
| 1220 | 10975477 | Group 2 (n = 5) showed unimpaired intracellular cytokine levels and responded to IA with a heterogeneous pattern of changes in TNF-alpha, IL-2, IFN-gamma, and IL-4 production, but these alterations were smaller than those in Group 1. |
| 1221 | 10975477 | Intracellular cytokine staining and flow cytometry were used to investigate whether immunoadsorption (IA) of immunoglobulins alters intracytoplasmic cytokine production in CD4+ and CD8+ T cells from the blood of patients with refractory rheumatoid arthritis (n = 7), membrane proliferative glomerulonephritis (n = 1), and Goodpasture's syndrome (n = 1). |
| 1222 | 10975477 | Four patients (Group 1) showed severely depressed production of TNF-alpha, IL-2, IFN-gamma, and IL-4 by CD4+ and CD8+ T cells and responded to 3 IA sessions with significant increases in CD4+TNF-alpha+, CD4+IL-2+, and CD8+IL-2+ T cells. |
| 1223 | 10975477 | Also, a tendency toward increased percentage levels of CD4+ T cells producing IFN-gamma or IL-4 and of CD8+ T cells producing either TNF-alpha or IFN-gamma was seen, but due to the small number of patients investigated, these differences did not attain statistic significance. |
| 1224 | 10975477 | Group 2 (n = 5) showed unimpaired intracellular cytokine levels and responded to IA with a heterogeneous pattern of changes in TNF-alpha, IL-2, IFN-gamma, and IL-4 production, but these alterations were smaller than those in Group 1. |
| 1225 | 10975477 | Intracellular cytokine staining and flow cytometry were used to investigate whether immunoadsorption (IA) of immunoglobulins alters intracytoplasmic cytokine production in CD4+ and CD8+ T cells from the blood of patients with refractory rheumatoid arthritis (n = 7), membrane proliferative glomerulonephritis (n = 1), and Goodpasture's syndrome (n = 1). |
| 1226 | 10975477 | Four patients (Group 1) showed severely depressed production of TNF-alpha, IL-2, IFN-gamma, and IL-4 by CD4+ and CD8+ T cells and responded to 3 IA sessions with significant increases in CD4+TNF-alpha+, CD4+IL-2+, and CD8+IL-2+ T cells. |
| 1227 | 10975477 | Also, a tendency toward increased percentage levels of CD4+ T cells producing IFN-gamma or IL-4 and of CD8+ T cells producing either TNF-alpha or IFN-gamma was seen, but due to the small number of patients investigated, these differences did not attain statistic significance. |
| 1228 | 10975477 | Group 2 (n = 5) showed unimpaired intracellular cytokine levels and responded to IA with a heterogeneous pattern of changes in TNF-alpha, IL-2, IFN-gamma, and IL-4 production, but these alterations were smaller than those in Group 1. |
| 1229 | 11005626 | After 40-hour incubation, the concentrations of the cytokines produced (IFN-gamma, IL-4, IL-10, IL-12) in the culture supernatants were measured by ELISA (Endogen, USA). |
| 1230 | 11005626 | The MNC cultures from patients with GD produced significantly less IL-12 and significantly more IL-10 and IL-4 than MNC cultures from healthy controls. |
| 1231 | 11005626 | After 40-hour incubation, the concentrations of the cytokines produced (IFN-gamma, IL-4, IL-10, IL-12) in the culture supernatants were measured by ELISA (Endogen, USA). |
| 1232 | 11005626 | The MNC cultures from patients with GD produced significantly less IL-12 and significantly more IL-10 and IL-4 than MNC cultures from healthy controls. |
| 1233 | 11050183 | Autoimmune insulin-dependent diabetes mellitus (IDDM) occurs spontaneously in mice-bearing transgenes encoding the influenza hemagglutinin under the control of the rat insulin promoter and a T cell receptor specific for an hemagglutinin peptide associated with I-E(d). |
| 1234 | 11050183 | Such "double transgenic" mice expressing wild-type or targeted IL-4Ralpha genes were examined for the onset of IDDM. |
| 1235 | 11050183 | Thus, the inability to respond to IL-4 and/or IL-13 protects mice against IDDM in this model of autoimmunity. |
| 1236 | 11078447 | Testicular sertoli cells protect islet beta-cells from autoimmune destruction in NOD mice by a transforming growth factor-beta1-dependent mechanism. |
| 1237 | 11078447 | The aim of this study was to determine whether Fas ligand (FasL) and/or transforming growth factor (TGF)-beta, immunoregulatory proteins produced by Sertoli cells, might mediate the protective effects of these cells against autoimmune destruction of islet beta-cells. |
| 1238 | 11078447 | Immunohistochemical examination of Sertoli cell grafts in normoglycemic mice revealed that TGF-beta1 expression by Sertoli cells remained high, whereas FasL expression by Sertoli cells decreased progressively posttransplantation. |
| 1239 | 11078447 | Islet graft destruction in anti-TGF-beta1-treated mice was associated with increases in interferon (IFN)-gamma-producing cells and decreases in interleukin (IL)-4-producing cells in the islet grafts. |
| 1240 | 11078447 | We conclude that 1) Sertoli cell production of TGF-beta1, not FasL, protects islet beta-cells from autoimmune destruction and 2) TGF-beta1 diverts islet-infiltrating cells from a beta-cell-destructive (IFN-gamma+) phenotype to a nondestructive (IL-4+) phenotype. |
| 1241 | 11078447 | Testicular sertoli cells protect islet beta-cells from autoimmune destruction in NOD mice by a transforming growth factor-beta1-dependent mechanism. |
| 1242 | 11078447 | The aim of this study was to determine whether Fas ligand (FasL) and/or transforming growth factor (TGF)-beta, immunoregulatory proteins produced by Sertoli cells, might mediate the protective effects of these cells against autoimmune destruction of islet beta-cells. |
| 1243 | 11078447 | Immunohistochemical examination of Sertoli cell grafts in normoglycemic mice revealed that TGF-beta1 expression by Sertoli cells remained high, whereas FasL expression by Sertoli cells decreased progressively posttransplantation. |
| 1244 | 11078447 | Islet graft destruction in anti-TGF-beta1-treated mice was associated with increases in interferon (IFN)-gamma-producing cells and decreases in interleukin (IL)-4-producing cells in the islet grafts. |
| 1245 | 11078447 | We conclude that 1) Sertoli cell production of TGF-beta1, not FasL, protects islet beta-cells from autoimmune destruction and 2) TGF-beta1 diverts islet-infiltrating cells from a beta-cell-destructive (IFN-gamma+) phenotype to a nondestructive (IL-4+) phenotype. |
| 1246 | 11086068 | We set up an adoptive transfer model in which the recipients were transgenic mice expressing influenza virus hemagglutinin (HA) specifically in their pancreatic ss islet cells (rat insulin promoter-HA mice) and islet-specific Tc1 and Tc2 cells were generated in vitro from HA-specific CD8(+) cells of TCR transgenic mice (CL4-TCR mice). |
| 1247 | 11086068 | Highly polarized Tc2 cells generated in the presence of IL-4, IL-10, and anti-IFN-gamma mAb had a relatively low, but definite, diabetogenic potential. |
| 1248 | 11092695 | Presence of interleukin 4 or interleukin 10, but not both cytokines, in pancreatic tissue of two patients with recently diagnosed diabetes mellitus type I. |
| 1249 | 11092695 | However, IL-4 (but not IL-10) cDNA, was amplified from the pancreas of Case 1. |
| 1250 | 11092695 | Conversely, IL-10 (but not IL-4) cDNA was amplified from the the pancreas of Case 2. |
| 1251 | 11092695 | The control pancreas yielded specific signals for both IL-4 and IL-10. |
| 1252 | 11092695 | Moreover, together with previous observations, our findings raise the possibility that the lack of both IL-4 and IL-10 may be associated with the development of IDDM in humans. |
| 1253 | 11092695 | Presence of interleukin 4 or interleukin 10, but not both cytokines, in pancreatic tissue of two patients with recently diagnosed diabetes mellitus type I. |
| 1254 | 11092695 | However, IL-4 (but not IL-10) cDNA, was amplified from the pancreas of Case 1. |
| 1255 | 11092695 | Conversely, IL-10 (but not IL-4) cDNA was amplified from the the pancreas of Case 2. |
| 1256 | 11092695 | The control pancreas yielded specific signals for both IL-4 and IL-10. |
| 1257 | 11092695 | Moreover, together with previous observations, our findings raise the possibility that the lack of both IL-4 and IL-10 may be associated with the development of IDDM in humans. |
| 1258 | 11092695 | Presence of interleukin 4 or interleukin 10, but not both cytokines, in pancreatic tissue of two patients with recently diagnosed diabetes mellitus type I. |
| 1259 | 11092695 | However, IL-4 (but not IL-10) cDNA, was amplified from the pancreas of Case 1. |
| 1260 | 11092695 | Conversely, IL-10 (but not IL-4) cDNA was amplified from the the pancreas of Case 2. |
| 1261 | 11092695 | The control pancreas yielded specific signals for both IL-4 and IL-10. |
| 1262 | 11092695 | Moreover, together with previous observations, our findings raise the possibility that the lack of both IL-4 and IL-10 may be associated with the development of IDDM in humans. |
| 1263 | 11092695 | Presence of interleukin 4 or interleukin 10, but not both cytokines, in pancreatic tissue of two patients with recently diagnosed diabetes mellitus type I. |
| 1264 | 11092695 | However, IL-4 (but not IL-10) cDNA, was amplified from the pancreas of Case 1. |
| 1265 | 11092695 | Conversely, IL-10 (but not IL-4) cDNA was amplified from the the pancreas of Case 2. |
| 1266 | 11092695 | The control pancreas yielded specific signals for both IL-4 and IL-10. |
| 1267 | 11092695 | Moreover, together with previous observations, our findings raise the possibility that the lack of both IL-4 and IL-10 may be associated with the development of IDDM in humans. |
| 1268 | 11092695 | Presence of interleukin 4 or interleukin 10, but not both cytokines, in pancreatic tissue of two patients with recently diagnosed diabetes mellitus type I. |
| 1269 | 11092695 | However, IL-4 (but not IL-10) cDNA, was amplified from the pancreas of Case 1. |
| 1270 | 11092695 | Conversely, IL-10 (but not IL-4) cDNA was amplified from the the pancreas of Case 2. |
| 1271 | 11092695 | The control pancreas yielded specific signals for both IL-4 and IL-10. |
| 1272 | 11092695 | Moreover, together with previous observations, our findings raise the possibility that the lack of both IL-4 and IL-10 may be associated with the development of IDDM in humans. |
| 1273 | 11092698 | Dual-label immunohistochemical study of interleukin-4-and interferon-gamma-expressing cells within the pancreas of the NOD mouse during disease acceleration with cyclophosphamide. |
| 1274 | 11092698 | Beta cell destruction has been shown to occur when rodent or human islets are exposed in vitro to inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). |
| 1275 | 11092698 | Other cytokines such as interleukin-4 (IL-4) or interleukin-10 (IL-10), when given to NOD mice, prevent insulin-dependent diabetes mellitus (IDDM). |
| 1276 | 11092698 | In this study, we have employed immunofluorescence histochemistry to study the expression of IFN-gamma and IL-4 in the pancreas of female NOD mice at various time-points (days 0, 4, 7, 11 and at onset of diabetes) following disease acceleration with cyclophosphamide (Cy). |
| 1277 | 11092698 | Our results demonstrate that during Cy-induced diabetes, there is increasing expression of both IL-4 and IFN-gamma in specific immune cells within the inflamed islets in the late prediabetic stage and at onset of diabetes. |
| 1278 | 11092698 | Dual-label immunohistochemical study of interleukin-4-and interferon-gamma-expressing cells within the pancreas of the NOD mouse during disease acceleration with cyclophosphamide. |
| 1279 | 11092698 | Beta cell destruction has been shown to occur when rodent or human islets are exposed in vitro to inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). |
| 1280 | 11092698 | Other cytokines such as interleukin-4 (IL-4) or interleukin-10 (IL-10), when given to NOD mice, prevent insulin-dependent diabetes mellitus (IDDM). |
| 1281 | 11092698 | In this study, we have employed immunofluorescence histochemistry to study the expression of IFN-gamma and IL-4 in the pancreas of female NOD mice at various time-points (days 0, 4, 7, 11 and at onset of diabetes) following disease acceleration with cyclophosphamide (Cy). |
| 1282 | 11092698 | Our results demonstrate that during Cy-induced diabetes, there is increasing expression of both IL-4 and IFN-gamma in specific immune cells within the inflamed islets in the late prediabetic stage and at onset of diabetes. |
| 1283 | 11092698 | Dual-label immunohistochemical study of interleukin-4-and interferon-gamma-expressing cells within the pancreas of the NOD mouse during disease acceleration with cyclophosphamide. |
| 1284 | 11092698 | Beta cell destruction has been shown to occur when rodent or human islets are exposed in vitro to inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). |
| 1285 | 11092698 | Other cytokines such as interleukin-4 (IL-4) or interleukin-10 (IL-10), when given to NOD mice, prevent insulin-dependent diabetes mellitus (IDDM). |
| 1286 | 11092698 | In this study, we have employed immunofluorescence histochemistry to study the expression of IFN-gamma and IL-4 in the pancreas of female NOD mice at various time-points (days 0, 4, 7, 11 and at onset of diabetes) following disease acceleration with cyclophosphamide (Cy). |
| 1287 | 11092698 | Our results demonstrate that during Cy-induced diabetes, there is increasing expression of both IL-4 and IFN-gamma in specific immune cells within the inflamed islets in the late prediabetic stage and at onset of diabetes. |
| 1288 | 11092698 | Dual-label immunohistochemical study of interleukin-4-and interferon-gamma-expressing cells within the pancreas of the NOD mouse during disease acceleration with cyclophosphamide. |
| 1289 | 11092698 | Beta cell destruction has been shown to occur when rodent or human islets are exposed in vitro to inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). |
| 1290 | 11092698 | Other cytokines such as interleukin-4 (IL-4) or interleukin-10 (IL-10), when given to NOD mice, prevent insulin-dependent diabetes mellitus (IDDM). |
| 1291 | 11092698 | In this study, we have employed immunofluorescence histochemistry to study the expression of IFN-gamma and IL-4 in the pancreas of female NOD mice at various time-points (days 0, 4, 7, 11 and at onset of diabetes) following disease acceleration with cyclophosphamide (Cy). |
| 1292 | 11092698 | Our results demonstrate that during Cy-induced diabetes, there is increasing expression of both IL-4 and IFN-gamma in specific immune cells within the inflamed islets in the late prediabetic stage and at onset of diabetes. |
| 1293 | 11141336 | NOD GM + IL-4 DC produced lower amounts of IL-12 p70 following CD40 ligation or LPS stimulation in the presence of IFN-gamma than DC from other strains, although similar levels of IL-6 and NO were produced by all strains. |
| 1294 | 11141336 | The low amounts of IL-12 p70 produced by GM + IL-4 DC are despite a more mature DC phenotype observed in NOD mice. |
| 1295 | 11141336 | NOD GM + IL-4 DC produced lower amounts of IL-12 p70 following CD40 ligation or LPS stimulation in the presence of IFN-gamma than DC from other strains, although similar levels of IL-6 and NO were produced by all strains. |
| 1296 | 11141336 | The low amounts of IL-12 p70 produced by GM + IL-4 DC are despite a more mature DC phenotype observed in NOD mice. |
| 1297 | 11145720 | Numerous immunostimulatory protocols inhibit the development of T cell-mediated autoimmune insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse model. |
| 1298 | 11145720 | Many of these protocols, including treatment with the nonspecific immunostimulatory agents CFA or bacillus Calmette-Guérin (BCG) vaccine, have been reported to mediate protection by skewing the pattern of cytokines produced by pancreatic beta-cell autoreactive T cells from a Th1 (IFN-gamma) to a Th2 (IL-4 and IL-10) profile. |
| 1299 | 11145720 | To partially address this issue we produced NOD mice genetically deficient in IFN-gamma, IL-4, or IL-10. |
| 1300 | 11145720 | Additional experiments using these mice confirmed that CFA- or BCG-elicited diabetes protection is associated with a decreased IFN-gamma to IL-4 mRNA ratio within T cell-infiltrated pancreatic islets, but this is a secondary consequence rather than the cause of disease resistance. |
| 1301 | 11145720 | Unexpectedly, we also found that the ability of BCG and, to a lesser extent, CFA to inhibit IDDM development in standard NOD mice is actually dependent upon the presence of the Th1 cytokine, IFN-gamma. |
| 1302 | 11145720 | Numerous immunostimulatory protocols inhibit the development of T cell-mediated autoimmune insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse model. |
| 1303 | 11145720 | Many of these protocols, including treatment with the nonspecific immunostimulatory agents CFA or bacillus Calmette-Guérin (BCG) vaccine, have been reported to mediate protection by skewing the pattern of cytokines produced by pancreatic beta-cell autoreactive T cells from a Th1 (IFN-gamma) to a Th2 (IL-4 and IL-10) profile. |
| 1304 | 11145720 | To partially address this issue we produced NOD mice genetically deficient in IFN-gamma, IL-4, or IL-10. |
| 1305 | 11145720 | Additional experiments using these mice confirmed that CFA- or BCG-elicited diabetes protection is associated with a decreased IFN-gamma to IL-4 mRNA ratio within T cell-infiltrated pancreatic islets, but this is a secondary consequence rather than the cause of disease resistance. |
| 1306 | 11145720 | Unexpectedly, we also found that the ability of BCG and, to a lesser extent, CFA to inhibit IDDM development in standard NOD mice is actually dependent upon the presence of the Th1 cytokine, IFN-gamma. |
| 1307 | 11145720 | Numerous immunostimulatory protocols inhibit the development of T cell-mediated autoimmune insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse model. |
| 1308 | 11145720 | Many of these protocols, including treatment with the nonspecific immunostimulatory agents CFA or bacillus Calmette-Guérin (BCG) vaccine, have been reported to mediate protection by skewing the pattern of cytokines produced by pancreatic beta-cell autoreactive T cells from a Th1 (IFN-gamma) to a Th2 (IL-4 and IL-10) profile. |
| 1309 | 11145720 | To partially address this issue we produced NOD mice genetically deficient in IFN-gamma, IL-4, or IL-10. |
| 1310 | 11145720 | Additional experiments using these mice confirmed that CFA- or BCG-elicited diabetes protection is associated with a decreased IFN-gamma to IL-4 mRNA ratio within T cell-infiltrated pancreatic islets, but this is a secondary consequence rather than the cause of disease resistance. |
| 1311 | 11145720 | Unexpectedly, we also found that the ability of BCG and, to a lesser extent, CFA to inhibit IDDM development in standard NOD mice is actually dependent upon the presence of the Th1 cytokine, IFN-gamma. |
| 1312 | 11160264 | In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4. |
| 1313 | 11160264 | Intramuscular injection of pDNA encoding GAD65-IgGFc and IL-4 effectively prevented diabetes in NOD mice treated at early or late preclinical stages of IDDM. |
| 1314 | 11160264 | This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes. |
| 1315 | 11160264 | Importantly, GAD65-specific immune deviation was dependent on pDNA-encoded IL-4. |
| 1316 | 11160264 | In fact, GAD65-specific Th1 cell reactivity was significantly enhanced in animals immunized with pDNA encoding only GAD65-IgGFc. |
| 1317 | 11160264 | In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4. |
| 1318 | 11160264 | Intramuscular injection of pDNA encoding GAD65-IgGFc and IL-4 effectively prevented diabetes in NOD mice treated at early or late preclinical stages of IDDM. |
| 1319 | 11160264 | This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes. |
| 1320 | 11160264 | Importantly, GAD65-specific immune deviation was dependent on pDNA-encoded IL-4. |
| 1321 | 11160264 | In fact, GAD65-specific Th1 cell reactivity was significantly enhanced in animals immunized with pDNA encoding only GAD65-IgGFc. |
| 1322 | 11160264 | In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4. |
| 1323 | 11160264 | Intramuscular injection of pDNA encoding GAD65-IgGFc and IL-4 effectively prevented diabetes in NOD mice treated at early or late preclinical stages of IDDM. |
| 1324 | 11160264 | This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes. |
| 1325 | 11160264 | Importantly, GAD65-specific immune deviation was dependent on pDNA-encoded IL-4. |
| 1326 | 11160264 | In fact, GAD65-specific Th1 cell reactivity was significantly enhanced in animals immunized with pDNA encoding only GAD65-IgGFc. |
| 1327 | 11160264 | In this study, we have investigated the use of plasmid DNA (pDNA) vaccination to elicit Th2 effector cell function in an Ag-specific manner and in turn prevent insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. pDNA recombinants were engineered encoding a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc, and IL-4. |
| 1328 | 11160264 | Intramuscular injection of pDNA encoding GAD65-IgGFc and IL-4 effectively prevented diabetes in NOD mice treated at early or late preclinical stages of IDDM. |
| 1329 | 11160264 | This protection was GAD65-specific since NOD mice immunized with pDNA encoding hen egg lysozyme-IgGFc and IL-4 continued to develop diabetes. |
| 1330 | 11160264 | Importantly, GAD65-specific immune deviation was dependent on pDNA-encoded IL-4. |
| 1331 | 11160264 | In fact, GAD65-specific Th1 cell reactivity was significantly enhanced in animals immunized with pDNA encoding only GAD65-IgGFc. |
| 1332 | 11161975 | Among them, there is our previous report that pancreatic expression of IL-4 activated islet antigen-specific BDC2.5 T cells and rendered them able to trigger insulin-dependent diabetes mellitus in ins-IL-4/BDC2.5 mice (Mueller et al., Immunity, 7, 1997). |
| 1333 | 11175852 | Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses. |
| 1334 | 11175852 | IL-4-influenced DC produce distinct effects on CD8+ T cells depending on their state of activation. |
| 1335 | 11175852 | Our findings demonstrate that B7.2 induces expansion of CD8+ T cells and B7.1 governs their acquisition of cytolytic activity. |
| 1336 | 11175852 | Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses. |
| 1337 | 11175852 | IL-4-influenced DC produce distinct effects on CD8+ T cells depending on their state of activation. |
| 1338 | 11175852 | Our findings demonstrate that B7.2 induces expansion of CD8+ T cells and B7.1 governs their acquisition of cytolytic activity. |
| 1339 | 11207247 | CD4(+) T cells arise spontaneously in young NOD mice to an apparently dominant determinant found within the GAD65 peptide 530--543 (p530); however, T cells to the overlapping determinant 524-538 (p524) dominate the response only after immunization with GAD65(524--543). |
| 1340 | 11207247 | T cell clones and hybridomas from both of these T cell groups were responsive to APC pulsed with GAD65(524--543) or whole rGAD65. p524-reactive cells appeared to be regulatory upon adoptive transfer into young NOD mice and could inhibit insulin-dependent diabetes mellitus development, although they were unable to produce IL-4, IL-10, or TGF beta upon antigenic challenge. |
| 1341 | 11222507 | CD28 co-stimulation restores T cell responsiveness in NOD mice by overcoming deficiencies in Rac-1/p38 mitogen-activated protein kinase signaling and IL-2 and IL-4 gene transcription. |
| 1342 | 11222507 | Neonatal CD28 co-stimulation reverses T cell hyporesponsiveness and protects NOD mice from diabetes by an IL-4-mediated mechanism, indicating that a deficiency in TCR signaling may be overcome by CD28/B7-2 co-stimulation in NOD T cells. |
| 1343 | 11222507 | To investigate which co-stimulation-induced signaling events mediate this protection, we analyzed the activity of Ras, Rac-1, mitogen-activated protein kinases (MAPK) and several transcription factors in TCR-activated NOD T cells in the presence or absence of CD28 co-stimulation. |
| 1344 | 11222507 | We show that CD28 co-stimulation restores normal TCR-induced activation of Rac-1 and p38 MAPK in NOD T cells. |
| 1345 | 11222507 | Deficiencies in TCR-induced nuclear expression of activating protein (AP)-1 binding proteins as well as activation of AP-1 and NF-AT in the IL-2 and IL-4 P1 promoters are also corrected by CD28 co-stimulation. |
| 1346 | 11222507 | Thus, CD28 co-stimulation reverses NOD T cell hyporesponsiveness by restoring TCR signaling leading to the activation of AP-1 and NF-AT during IL-2 and IL-4 gene transcription. |
| 1347 | 11222507 | CD28 co-stimulation restores T cell responsiveness in NOD mice by overcoming deficiencies in Rac-1/p38 mitogen-activated protein kinase signaling and IL-2 and IL-4 gene transcription. |
| 1348 | 11222507 | Neonatal CD28 co-stimulation reverses T cell hyporesponsiveness and protects NOD mice from diabetes by an IL-4-mediated mechanism, indicating that a deficiency in TCR signaling may be overcome by CD28/B7-2 co-stimulation in NOD T cells. |
| 1349 | 11222507 | To investigate which co-stimulation-induced signaling events mediate this protection, we analyzed the activity of Ras, Rac-1, mitogen-activated protein kinases (MAPK) and several transcription factors in TCR-activated NOD T cells in the presence or absence of CD28 co-stimulation. |
| 1350 | 11222507 | We show that CD28 co-stimulation restores normal TCR-induced activation of Rac-1 and p38 MAPK in NOD T cells. |
| 1351 | 11222507 | Deficiencies in TCR-induced nuclear expression of activating protein (AP)-1 binding proteins as well as activation of AP-1 and NF-AT in the IL-2 and IL-4 P1 promoters are also corrected by CD28 co-stimulation. |
| 1352 | 11222507 | Thus, CD28 co-stimulation reverses NOD T cell hyporesponsiveness by restoring TCR signaling leading to the activation of AP-1 and NF-AT during IL-2 and IL-4 gene transcription. |
| 1353 | 11222507 | CD28 co-stimulation restores T cell responsiveness in NOD mice by overcoming deficiencies in Rac-1/p38 mitogen-activated protein kinase signaling and IL-2 and IL-4 gene transcription. |
| 1354 | 11222507 | Neonatal CD28 co-stimulation reverses T cell hyporesponsiveness and protects NOD mice from diabetes by an IL-4-mediated mechanism, indicating that a deficiency in TCR signaling may be overcome by CD28/B7-2 co-stimulation in NOD T cells. |
| 1355 | 11222507 | To investigate which co-stimulation-induced signaling events mediate this protection, we analyzed the activity of Ras, Rac-1, mitogen-activated protein kinases (MAPK) and several transcription factors in TCR-activated NOD T cells in the presence or absence of CD28 co-stimulation. |
| 1356 | 11222507 | We show that CD28 co-stimulation restores normal TCR-induced activation of Rac-1 and p38 MAPK in NOD T cells. |
| 1357 | 11222507 | Deficiencies in TCR-induced nuclear expression of activating protein (AP)-1 binding proteins as well as activation of AP-1 and NF-AT in the IL-2 and IL-4 P1 promoters are also corrected by CD28 co-stimulation. |
| 1358 | 11222507 | Thus, CD28 co-stimulation reverses NOD T cell hyporesponsiveness by restoring TCR signaling leading to the activation of AP-1 and NF-AT during IL-2 and IL-4 gene transcription. |
| 1359 | 11222507 | CD28 co-stimulation restores T cell responsiveness in NOD mice by overcoming deficiencies in Rac-1/p38 mitogen-activated protein kinase signaling and IL-2 and IL-4 gene transcription. |
| 1360 | 11222507 | Neonatal CD28 co-stimulation reverses T cell hyporesponsiveness and protects NOD mice from diabetes by an IL-4-mediated mechanism, indicating that a deficiency in TCR signaling may be overcome by CD28/B7-2 co-stimulation in NOD T cells. |
| 1361 | 11222507 | To investigate which co-stimulation-induced signaling events mediate this protection, we analyzed the activity of Ras, Rac-1, mitogen-activated protein kinases (MAPK) and several transcription factors in TCR-activated NOD T cells in the presence or absence of CD28 co-stimulation. |
| 1362 | 11222507 | We show that CD28 co-stimulation restores normal TCR-induced activation of Rac-1 and p38 MAPK in NOD T cells. |
| 1363 | 11222507 | Deficiencies in TCR-induced nuclear expression of activating protein (AP)-1 binding proteins as well as activation of AP-1 and NF-AT in the IL-2 and IL-4 P1 promoters are also corrected by CD28 co-stimulation. |
| 1364 | 11222507 | Thus, CD28 co-stimulation reverses NOD T cell hyporesponsiveness by restoring TCR signaling leading to the activation of AP-1 and NF-AT during IL-2 and IL-4 gene transcription. |
| 1365 | 11238616 | IL-4 mRNA levels are increased and IFN-gamma mRNA levels decreased in islets from diabetes-free V alpha 14-J alpha 281 transgenic NOD mice; the IgG1/IgG2c ratio of autoantibodies against glutamic acid decarboxylase is also increased in these mice. |
| 1366 | 11238667 | Chronic inflammatory autoimmune diseases such as diabetes, experimental autoimmune encephalomyelitis, and collagen-induced arthritis (CIA) are associated with type 1 (Th1, Tc1) T cell-dependent responses against autoantigens. |
| 1367 | 11238667 | In response to IL-2 binding, this chimeric receptor transduces IL-4-specific signals and dramatically enhances type 2 responses. |
| 1368 | 11238667 | The aggravated disease in transgenic mice was associated with an increase in type 2 cytokines (IL-4, IL-5, IL-10) and an increase in collagen-specific IgG1 levels. |
| 1369 | 11238667 | Chronic inflammatory autoimmune diseases such as diabetes, experimental autoimmune encephalomyelitis, and collagen-induced arthritis (CIA) are associated with type 1 (Th1, Tc1) T cell-dependent responses against autoantigens. |
| 1370 | 11238667 | In response to IL-2 binding, this chimeric receptor transduces IL-4-specific signals and dramatically enhances type 2 responses. |
| 1371 | 11238667 | The aggravated disease in transgenic mice was associated with an increase in type 2 cytokines (IL-4, IL-5, IL-10) and an increase in collagen-specific IgG1 levels. |
| 1372 | 11246870 | We demonstrate here that recombinant adeno-associated virus (rAAV) serotype 2, a vector that can overcome these limitations, effectively transduces both human and murine pancreatic islet cells with reporter genes as well as potentially important immunoregulatory cytokine genes (interleukin-4, interleukin-10), although a very high multiplicity of infection (10,000 infectious units/islet equivalent) was required. |
| 1373 | 11269889 | In this study, we focused on the cytotoxic activity of peripheral lymphocytes in patients with type 1 DM against the peptides of glutamic acid decarboxylase (GAD) and insulin, which can bind MHC class 1 A24. |
| 1374 | 11269889 | The effector cells were cultured with peptides, IL-2 and IL-7, restimulated weekly by autologous antigen presenting cells, which were cultured with IL-4 and GM-CSF. |
| 1375 | 11269889 | The results showed that cytotoxicity against insulin peptide binding to MHC class I A24 was observed in lymphocytes of four out of ten patients with type 1 DM. |
| 1376 | 11269889 | Cytotoxicity against GAD peptide which bind MHC class I A24 was not observed in seven patients. |
| 1377 | 11269889 | None of healthy controls showed cytotoxicity against GAD or insulin peptides was observed. |
| 1378 | 11269889 | This is the first report describing the cytotoxic activity of CD8+ T lymphocytes against insulin in type 1 DM. |
| 1379 | 11309160 | The aim of this study was to evaluate possible changes in the circulating levels of interferon (IFN)-gamma, interleukin (IL)-4 and transforming growth factor (TGF)-beta in association with the autoimmune process leading to type 1 diabetes. |
| 1380 | 11309160 | Newly diagnosed diabetic children had lower levels of IFN-gamma, IL-4 and TGF-beta 1 signals compared to their age- and sex-matched controls (P < 0.02, P < 0.005 and P < 0.005, respectively) and also the autoantibody-positive subjects had significantly lower levels of IL-4 and TGF-beta 1 in comparison with their matched controls (P = 0.0013 and P = 0.012). |
| 1381 | 11309160 | Our results suggest a systemic bias towards reduced production of T-helper cell type 2 cytokines (IL-4 and TGF-beta 1) during the autoimmune process, but there was also a reduced level of IFN-gamma expression in the periphery at the onset of clinical diabetes. |
| 1382 | 11309160 | The aim of this study was to evaluate possible changes in the circulating levels of interferon (IFN)-gamma, interleukin (IL)-4 and transforming growth factor (TGF)-beta in association with the autoimmune process leading to type 1 diabetes. |
| 1383 | 11309160 | Newly diagnosed diabetic children had lower levels of IFN-gamma, IL-4 and TGF-beta 1 signals compared to their age- and sex-matched controls (P < 0.02, P < 0.005 and P < 0.005, respectively) and also the autoantibody-positive subjects had significantly lower levels of IL-4 and TGF-beta 1 in comparison with their matched controls (P = 0.0013 and P = 0.012). |
| 1384 | 11309160 | Our results suggest a systemic bias towards reduced production of T-helper cell type 2 cytokines (IL-4 and TGF-beta 1) during the autoimmune process, but there was also a reduced level of IFN-gamma expression in the periphery at the onset of clinical diabetes. |
| 1385 | 11309160 | The aim of this study was to evaluate possible changes in the circulating levels of interferon (IFN)-gamma, interleukin (IL)-4 and transforming growth factor (TGF)-beta in association with the autoimmune process leading to type 1 diabetes. |
| 1386 | 11309160 | Newly diagnosed diabetic children had lower levels of IFN-gamma, IL-4 and TGF-beta 1 signals compared to their age- and sex-matched controls (P < 0.02, P < 0.005 and P < 0.005, respectively) and also the autoantibody-positive subjects had significantly lower levels of IL-4 and TGF-beta 1 in comparison with their matched controls (P = 0.0013 and P = 0.012). |
| 1387 | 11309160 | Our results suggest a systemic bias towards reduced production of T-helper cell type 2 cytokines (IL-4 and TGF-beta 1) during the autoimmune process, but there was also a reduced level of IFN-gamma expression in the periphery at the onset of clinical diabetes. |
| 1388 | 11311961 | The treatment with copper sulfate significantly decreased blood glucose levels, levels of lipid peroxidation and mRNA expression of the enzyme iNOS and the cytokines IFN-gamma and IL-4. |
| 1389 | 11312119 | IL-18 is a potent proinflammatory cytokine able to induce IFNgamma, GM-CSF, TNFalpha and IL-1 in immunocompetent cells, to activate killing by lymphocytes, and to up-regulate the expression of certain chemokine receptors. |
| 1390 | 11312119 | Moreover, IL-18 also induces IL-13 and/or IL-4 production by NK cells, mast cells and basophils. |
| 1391 | 11349735 | Transplanted NOD-B2 m-/- islets were surrounded by a nondestructive periinsular infiltrate that expressed interleukin-4 in addition to interferon-gamma. |
| 1392 | 11359854 | Several studies have provided indirect evidence in support of a role for beta cell-specific Th2 cells in regulating insulin-dependent diabetes (IDDM). |
| 1393 | 11359854 | Adoptive transfer of a GAD65-specific Th2 cell clone (characterized by the secretion of IL-4, IL-5, and IL-10, but not IFN-gamma or TGF-beta) into 2- or 12-wk-old NOD female recipients prevented the progression of insulitis and subsequent development of overt IDDM. |
| 1394 | 11359854 | The immunoregulatory function of a given Th cell clone was dependent on the relative levels of IFN-gamma vs IL-4 and IL-10 secreted. |
| 1395 | 11359854 | Several studies have provided indirect evidence in support of a role for beta cell-specific Th2 cells in regulating insulin-dependent diabetes (IDDM). |
| 1396 | 11359854 | Adoptive transfer of a GAD65-specific Th2 cell clone (characterized by the secretion of IL-4, IL-5, and IL-10, but not IFN-gamma or TGF-beta) into 2- or 12-wk-old NOD female recipients prevented the progression of insulitis and subsequent development of overt IDDM. |
| 1397 | 11359854 | The immunoregulatory function of a given Th cell clone was dependent on the relative levels of IFN-gamma vs IL-4 and IL-10 secreted. |
| 1398 | 11390999 | The acceleration of disease did not seem to result from changes in the T helper (Th)1/Th2 balance because lymphocytes purified from lymphoid organs and pancreatic islets of wild-type and CD1d-null mice secreted equivalent amounts of IFN-gamma and IL-4 after stimulation. |
| 1399 | 11409710 | NOD/LtJ and NOD/Bom mice were found significantly to upregulate pancreatic IL-12p40 and IL-18 expression after cyclophosphamide treatment, followed by an increase in IFN-gamma mRNA levels. |
| 1400 | 11409710 | In contrast, the two MHC-haplotype H-2nbl expressing strains either up-regulated neither IL-12/IL-18 nor IFN-gamma gene expression. |
| 1401 | 11409710 | NOR mice progressed to IFN-gamma expression but exhibited sustained IL-4 gene expression. |
| 1402 | 11418698 | We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. |
| 1403 | 11418698 | Insulin was chosen based on studies demonstrating that administration of insulin or insulin B chain by a variety of strategies prevents IDDM in NOD mice. |
| 1404 | 11418698 | Surprisingly, young NOD mice receiving i.m. injections of pDNA encoding insulin B chain-IgGFc with or without IL-4 exhibited an accelerated progression of insulitis and developed early diabetes. |
| 1405 | 11418698 | Exacerbation of IDDM correlated with an increased frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells in response to insulin B chain-specific peptides compared with untreated mice. |
| 1406 | 11418698 | In contrast, treatment with pDNAs encoding insulin A chain-IgGFc and IL-4 elicited a low frequency of IL-4-secreting Th cells and had no effect on the progression of IDDM. |
| 1407 | 11418698 | Vaccination with pDNAs encoding GAD65-IgGFc and IL-4, however, prevented IDDM. |
| 1408 | 11418698 | These results demonstrate that insulin- and GAD65-specific T cell reactivity induced by pDNA vaccination has distinct effects on the progression of IDDM. |
| 1409 | 11418698 | We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. |
| 1410 | 11418698 | Insulin was chosen based on studies demonstrating that administration of insulin or insulin B chain by a variety of strategies prevents IDDM in NOD mice. |
| 1411 | 11418698 | Surprisingly, young NOD mice receiving i.m. injections of pDNA encoding insulin B chain-IgGFc with or without IL-4 exhibited an accelerated progression of insulitis and developed early diabetes. |
| 1412 | 11418698 | Exacerbation of IDDM correlated with an increased frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells in response to insulin B chain-specific peptides compared with untreated mice. |
| 1413 | 11418698 | In contrast, treatment with pDNAs encoding insulin A chain-IgGFc and IL-4 elicited a low frequency of IL-4-secreting Th cells and had no effect on the progression of IDDM. |
| 1414 | 11418698 | Vaccination with pDNAs encoding GAD65-IgGFc and IL-4, however, prevented IDDM. |
| 1415 | 11418698 | These results demonstrate that insulin- and GAD65-specific T cell reactivity induced by pDNA vaccination has distinct effects on the progression of IDDM. |
| 1416 | 11418698 | We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. |
| 1417 | 11418698 | Insulin was chosen based on studies demonstrating that administration of insulin or insulin B chain by a variety of strategies prevents IDDM in NOD mice. |
| 1418 | 11418698 | Surprisingly, young NOD mice receiving i.m. injections of pDNA encoding insulin B chain-IgGFc with or without IL-4 exhibited an accelerated progression of insulitis and developed early diabetes. |
| 1419 | 11418698 | Exacerbation of IDDM correlated with an increased frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells in response to insulin B chain-specific peptides compared with untreated mice. |
| 1420 | 11418698 | In contrast, treatment with pDNAs encoding insulin A chain-IgGFc and IL-4 elicited a low frequency of IL-4-secreting Th cells and had no effect on the progression of IDDM. |
| 1421 | 11418698 | Vaccination with pDNAs encoding GAD65-IgGFc and IL-4, however, prevented IDDM. |
| 1422 | 11418698 | These results demonstrate that insulin- and GAD65-specific T cell reactivity induced by pDNA vaccination has distinct effects on the progression of IDDM. |
| 1423 | 11418698 | We previously demonstrated that administration of plasmid DNAs (pDNAs) encoding IL-4 and a fragment of glutamic acid decarboxylase 65 (GAD65) fused to IgGFc induces GAD65-specific Th2 cells and prevents insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. |
| 1424 | 11418698 | Insulin was chosen based on studies demonstrating that administration of insulin or insulin B chain by a variety of strategies prevents IDDM in NOD mice. |
| 1425 | 11418698 | Surprisingly, young NOD mice receiving i.m. injections of pDNA encoding insulin B chain-IgGFc with or without IL-4 exhibited an accelerated progression of insulitis and developed early diabetes. |
| 1426 | 11418698 | Exacerbation of IDDM correlated with an increased frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells in response to insulin B chain-specific peptides compared with untreated mice. |
| 1427 | 11418698 | In contrast, treatment with pDNAs encoding insulin A chain-IgGFc and IL-4 elicited a low frequency of IL-4-secreting Th cells and had no effect on the progression of IDDM. |
| 1428 | 11418698 | Vaccination with pDNAs encoding GAD65-IgGFc and IL-4, however, prevented IDDM. |
| 1429 | 11418698 | These results demonstrate that insulin- and GAD65-specific T cell reactivity induced by pDNA vaccination has distinct effects on the progression of IDDM. |
| 1430 | 11422905 | The mRNA expression for IL-12(p40), IL-18, and interferon (IFN)-gamma, but not IL-5, increased in the spleen in parallel with the development of insulitis. |
| 1431 | 11422905 | The treatment with MoAb to IL-12(p40) reduced the insulitis with diabetes which was associated with a decrease in the mRNA expression for IL-12(p40), IL-18 and IFN-gamma, and an increase of IL-4 mRNA expression in the spleen. |
| 1432 | 11422905 | The present study suggested that Th1-dominant systemic immune responses, being responsible for the development of autoimmune insulitis, might be induced by IL-12-induced and IL-18-activated mechanisms. |
| 1433 | 11466393 | Increased entry into the IFN-gamma effector pathway by CD4+ T cells selected by I-Ag7 on a nonobese diabetic versus C57BL/6 genetic background. |
| 1434 | 11466393 | IFN-gamma-mediated Th1 effects play a major role in the pathogenesis of autoimmune diabetes in nonobese diabetic (NOD) mice. |
| 1435 | 11466393 | We analyzed functional responses of CD4(+) T cells from NOD and B6.G7 MHC congenic mice, which share the H2(g7) MHC region but differ in their non-MHC genetic background. |
| 1436 | 11466393 | Despite comparable proliferative responses, NOD CD4(+) T cells had significantly increased IFN-gamma intracellular/extracellular protein and mRNA responses compared with B6.G7 T cells as measured by intracellular cytokine analysis, time resolved fluorometry, and RNase protection assays. |
| 1437 | 11466393 | The increased IFN-gamma production was not due to an increase in the amount of IFN-gamma produced per cell but to an increase in the number of NOD CD4(+) T cells entering the IFN-gamma-producing pathway. |
| 1438 | 11466393 | B6.G7 lymphoid cells demonstrated an absolute decrease in IFN-gamma mRNA, an increase in IL-4 mRNA production, and a significantly decreased IFN-gamma:IL-4 mRNA transcript ratio compared with NOD cells. |
| 1439 | 11466393 | CD4(+) T cells from C57BL6 mice also showed significantly decreased IFN-gamma production compared with CD4(+) T cells from NOD.H2(b) MHC-congenic mice (which have an H2(b) MHC region introgressed onto an NOD non-MHC background). |
| 1440 | 11466393 | Therefore, the NOD non-MHC background predisposes to a quantitatively increased IFN-gamma response, independent of MHC class II-mediated T cell repertoire selection, even when compared with a prototypical Th1 strain. |
| 1441 | 11489328 | Cell type specific and glucose responsive expression of interleukin-4 by using insulin promoter and water soluble lipopolymer. |
| 1442 | 11489328 | In this study, we constructed pRIP-IL4 in which the expression of interleukin-4 (IL-4) was driven by the rat insulin promoter. |
| 1443 | 11489328 | Cell type specific and glucose responsive expression of interleukin-4 by using insulin promoter and water soluble lipopolymer. |
| 1444 | 11489328 | In this study, we constructed pRIP-IL4 in which the expression of interleukin-4 (IL-4) was driven by the rat insulin promoter. |
| 1445 | 11490031 | Introduction of a disrupted IL-4 gene into the NOD-H2-E transgenic stock demonstrated that induction of this Th2 cytokine does not represent the IDDM protective immunoregulatory process mediated by H2-E expression. |
| 1446 | 11509644 | This was associated with a T2 shift in spleen, expansion of IL-4-producing and, to a lesser extent, of IFN-gamma-secreting T cells in pancreatic lymph nodes, as well as intermolecular Th2 epitope spreading to glutamic acid decarboxylase determinants. |
| 1447 | 11521435 | Ten cytokines (alpha-IFN, gamma-IFN, GM-CSF, TGF-beta 1, Il-1, Il-4, Il-6, Il-6sR, TNF alpha) were measured in the serum, lacrimal fluid, and vitreous and subretinal fluid collected during operations. |
| 1448 | 11521435 | The data indicate that excessive or insufficient local and/or systemic production of at least seven cytokines (TNF alpha, gamma-IFN, Il-6, Il-pR, alpha-IFN, Il-8, and RGF-beta 1) can affect the retinal involvement in the pathological process and development of proliferative retinopathy in patients with insulin-dependent diabetes mellitus. |
| 1449 | 11529910 | This response was characterized by an intensive increase in splenic IgG1 antibody secreting cells, a marked elevation in serum IgE levels, a substantial increase in splenic IL-4 mRNA, but a significant decrease in splenic IFN-gamma mRNA. |
| 1450 | 11533710 | Disease prevention correlated with the ability of alpha-GalCer to suppress interferon-gamma but not interleukin-4 production by NKT cells, to increase serum immunoglobulin E levels, and to promote the generation of islet autoantigen-specific Th2 cells. |
| 1451 | 11533711 | The immunoregulatory activity of natural killer T (NKT) cells is well documented, and both interleukin (IL)-4 and IL-10 secreted by NKT cells have important roles in mediating this activity. |
| 1452 | 11590186 | Here, we completely blocked adoptive transfer of diabetes and reduced spontaneous disease incidence from 71% to 17% by simultaneously administering a combination of antibodies directed against alpha4, beta2, and beta7 integrins and their ligands VCAM-1, MAdCAM-1, and ICAM-1 for 52 and 28 days, respectively. |
| 1453 | 11590186 | CD4 and CD8 T cells and macrophages were excluded from islets and remained entrapped in a peri-islet location as inactive exiles, no longer expressing normal levels of interferon-gamma, interleukin-4, and iNOS. |
| 1454 | 11591119 | Furthermore, ICAM-1(+/+) NOD mice showed an increase of IFN-gamma, interleukin (IL)-12p40 and IL-12p35 pancreatic mRNA levels, leading to an increased ratio of IFN-gamma: IL-4 and IL-12p40: IL-12p35 expression. |
| 1455 | 11591119 | In contrast, ICAM-1(-/-) NOD mice did not upregulate IFN-gamma or IL-12p40 gene expression but maintained IL-4 and increased IL-12p35 gene expression. |
| 1456 | 11591119 | Furthermore, ICAM-1(+/+) NOD mice showed an increase of IFN-gamma, interleukin (IL)-12p40 and IL-12p35 pancreatic mRNA levels, leading to an increased ratio of IFN-gamma: IL-4 and IL-12p40: IL-12p35 expression. |
| 1457 | 11591119 | In contrast, ICAM-1(-/-) NOD mice did not upregulate IFN-gamma or IL-12p40 gene expression but maintained IL-4 and increased IL-12p35 gene expression. |
| 1458 | 11592833 | Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in nonobese diabetic mice. |
| 1459 | 11592833 | Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet beta-cell destruction belong to the Th1 subset (producing IL-2 and IFN-gamma), whereas regulatory T cells are Th2 type (producing IL-4 and IL-10). |
| 1460 | 11592833 | Here, we evaluate the effect of combined delivery of plasmid DNA encoding IL-4 and IL-10 using a degradable, cationic polymeric carrier, poly[gamma-(4-aminobutyl)-L-glycolic acid] (PAGA), in nonobese diabetic (NOD) mice. |
| 1461 | 11592833 | In the liver of NOD mice, we detected mouse Il4 and Il10 mRNA 5 days after intravenous injection of both PAGA-Il4 and PAGA-Il10 plasmid complexes. |
| 1462 | 11592833 | Thus, combined administration of mouse Il4 and Il10 plasmids prevents the development of autoimmune diabetes in NOD mice. |
| 1463 | 11592833 | Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in nonobese diabetic mice. |
| 1464 | 11592833 | Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet beta-cell destruction belong to the Th1 subset (producing IL-2 and IFN-gamma), whereas regulatory T cells are Th2 type (producing IL-4 and IL-10). |
| 1465 | 11592833 | Here, we evaluate the effect of combined delivery of plasmid DNA encoding IL-4 and IL-10 using a degradable, cationic polymeric carrier, poly[gamma-(4-aminobutyl)-L-glycolic acid] (PAGA), in nonobese diabetic (NOD) mice. |
| 1466 | 11592833 | In the liver of NOD mice, we detected mouse Il4 and Il10 mRNA 5 days after intravenous injection of both PAGA-Il4 and PAGA-Il10 plasmid complexes. |
| 1467 | 11592833 | Thus, combined administration of mouse Il4 and Il10 plasmids prevents the development of autoimmune diabetes in NOD mice. |
| 1468 | 11592833 | Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in nonobese diabetic mice. |
| 1469 | 11592833 | Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet beta-cell destruction belong to the Th1 subset (producing IL-2 and IFN-gamma), whereas regulatory T cells are Th2 type (producing IL-4 and IL-10). |
| 1470 | 11592833 | Here, we evaluate the effect of combined delivery of plasmid DNA encoding IL-4 and IL-10 using a degradable, cationic polymeric carrier, poly[gamma-(4-aminobutyl)-L-glycolic acid] (PAGA), in nonobese diabetic (NOD) mice. |
| 1471 | 11592833 | In the liver of NOD mice, we detected mouse Il4 and Il10 mRNA 5 days after intravenous injection of both PAGA-Il4 and PAGA-Il10 plasmid complexes. |
| 1472 | 11592833 | Thus, combined administration of mouse Il4 and Il10 plasmids prevents the development of autoimmune diabetes in NOD mice. |
| 1473 | 11592833 | Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in nonobese diabetic mice. |
| 1474 | 11592833 | Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet beta-cell destruction belong to the Th1 subset (producing IL-2 and IFN-gamma), whereas regulatory T cells are Th2 type (producing IL-4 and IL-10). |
| 1475 | 11592833 | Here, we evaluate the effect of combined delivery of plasmid DNA encoding IL-4 and IL-10 using a degradable, cationic polymeric carrier, poly[gamma-(4-aminobutyl)-L-glycolic acid] (PAGA), in nonobese diabetic (NOD) mice. |
| 1476 | 11592833 | In the liver of NOD mice, we detected mouse Il4 and Il10 mRNA 5 days after intravenous injection of both PAGA-Il4 and PAGA-Il10 plasmid complexes. |
| 1477 | 11592833 | Thus, combined administration of mouse Il4 and Il10 plasmids prevents the development of autoimmune diabetes in NOD mice. |
| 1478 | 11592833 | Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in nonobese diabetic mice. |
| 1479 | 11592833 | Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet beta-cell destruction belong to the Th1 subset (producing IL-2 and IFN-gamma), whereas regulatory T cells are Th2 type (producing IL-4 and IL-10). |
| 1480 | 11592833 | Here, we evaluate the effect of combined delivery of plasmid DNA encoding IL-4 and IL-10 using a degradable, cationic polymeric carrier, poly[gamma-(4-aminobutyl)-L-glycolic acid] (PAGA), in nonobese diabetic (NOD) mice. |
| 1481 | 11592833 | In the liver of NOD mice, we detected mouse Il4 and Il10 mRNA 5 days after intravenous injection of both PAGA-Il4 and PAGA-Il10 plasmid complexes. |
| 1482 | 11592833 | Thus, combined administration of mouse Il4 and Il10 plasmids prevents the development of autoimmune diabetes in NOD mice. |
| 1483 | 11602650 | Although PDG does not block interleukin (IL)-2 production, it efficiently inhibits interleukin-2 receptor alpha-chain (IL-2Ralpha) expression, and this results in a disruption of the IL-2/IL-2R signaling pathway, on which a great part of the regulation of T cell activation depends. |
| 1484 | 11602650 | PDG blocks T cell differentiation into effector helper T cells secreting interferon-gamma and IL-4 as well as into effector cytotoxic T lymphocytes expressing perforin, which is at least in part resulting from inhibition of the IL-2/IL-2R signaling. |
| 1485 | 11602650 | In conclusion, our results demonstrate that PDG has a unique mode of action, namely, that it blocks T cell activation by inhibiting primarily IL-2Ralpha expression in the IL-2/IL-2R signaling, and show that this compound represents a promising immunosuppressant candidate for the treatment of autoimmune diseases. |
| 1486 | 11603866 | NKT cells respond to various external stimuli by an early burst of cytokines, including IL-4 and IFN-gamma. |
| 1487 | 11681488 | Induction of interferon-gamma and IL-4 production by mitogen and specific antigens in peripheral blood lymphocytes of Type 1 diabetes patients. |
| 1488 | 11681488 | In this study the cellular responses to pokeweed mitogen and a panel of specific antigens were analysed by measuring the production of IFN-gamma and IL-4 cytokines at the levels of mRNA expression (expression index=antigen/medium) and protein secretion in culture supernatants. |
| 1489 | 11681488 | Newly diagnosed diabetic patients had significantly higher IFN-gamma mRNA expression index (p<0.02) but also higher IL-4 mRNA expression index (p<0.05) in tetanus toxoid stimulated peripheral blood mononuclear cells compared to healthy controls. |
| 1490 | 11681488 | In conclusion, imbalance in both IFN-gamma and IL-4 mRNA levels was demonstrated between diabetic patients and healthy subjects. |
| 1491 | 11681488 | Induction of interferon-gamma and IL-4 production by mitogen and specific antigens in peripheral blood lymphocytes of Type 1 diabetes patients. |
| 1492 | 11681488 | In this study the cellular responses to pokeweed mitogen and a panel of specific antigens were analysed by measuring the production of IFN-gamma and IL-4 cytokines at the levels of mRNA expression (expression index=antigen/medium) and protein secretion in culture supernatants. |
| 1493 | 11681488 | Newly diagnosed diabetic patients had significantly higher IFN-gamma mRNA expression index (p<0.02) but also higher IL-4 mRNA expression index (p<0.05) in tetanus toxoid stimulated peripheral blood mononuclear cells compared to healthy controls. |
| 1494 | 11681488 | In conclusion, imbalance in both IFN-gamma and IL-4 mRNA levels was demonstrated between diabetic patients and healthy subjects. |
| 1495 | 11681488 | Induction of interferon-gamma and IL-4 production by mitogen and specific antigens in peripheral blood lymphocytes of Type 1 diabetes patients. |
| 1496 | 11681488 | In this study the cellular responses to pokeweed mitogen and a panel of specific antigens were analysed by measuring the production of IFN-gamma and IL-4 cytokines at the levels of mRNA expression (expression index=antigen/medium) and protein secretion in culture supernatants. |
| 1497 | 11681488 | Newly diagnosed diabetic patients had significantly higher IFN-gamma mRNA expression index (p<0.02) but also higher IL-4 mRNA expression index (p<0.05) in tetanus toxoid stimulated peripheral blood mononuclear cells compared to healthy controls. |
| 1498 | 11681488 | In conclusion, imbalance in both IFN-gamma and IL-4 mRNA levels was demonstrated between diabetic patients and healthy subjects. |
| 1499 | 11681488 | Induction of interferon-gamma and IL-4 production by mitogen and specific antigens in peripheral blood lymphocytes of Type 1 diabetes patients. |
| 1500 | 11681488 | In this study the cellular responses to pokeweed mitogen and a panel of specific antigens were analysed by measuring the production of IFN-gamma and IL-4 cytokines at the levels of mRNA expression (expression index=antigen/medium) and protein secretion in culture supernatants. |
| 1501 | 11681488 | Newly diagnosed diabetic patients had significantly higher IFN-gamma mRNA expression index (p<0.02) but also higher IL-4 mRNA expression index (p<0.05) in tetanus toxoid stimulated peripheral blood mononuclear cells compared to healthy controls. |
| 1502 | 11681488 | In conclusion, imbalance in both IFN-gamma and IL-4 mRNA levels was demonstrated between diabetic patients and healthy subjects. |
| 1503 | 11717448 | To test the feasibility of muscle-directed gene therapy to prevent type 1 diabetes, we developed recombinant adeno-associated virus (rAAV) vectors containing murine cDNAs for immunomodulatory cytokines IL-4 or IL-10. |
| 1504 | 11717448 | Skeletal muscle transduction of female NOD mice with IL-10, but not IL-4, completely abrogated diabetes. rAAV-IL-10 transduction attenuated the production of insulin autoantibodies, quantitatively reduced pancreatic insulitis, maintained islet insulin content, and altered splenocyte cytokine responses to mitogenic stimulation. |
| 1505 | 11717448 | To test the feasibility of muscle-directed gene therapy to prevent type 1 diabetes, we developed recombinant adeno-associated virus (rAAV) vectors containing murine cDNAs for immunomodulatory cytokines IL-4 or IL-10. |
| 1506 | 11717448 | Skeletal muscle transduction of female NOD mice with IL-10, but not IL-4, completely abrogated diabetes. rAAV-IL-10 transduction attenuated the production of insulin autoantibodies, quantitatively reduced pancreatic insulitis, maintained islet insulin content, and altered splenocyte cytokine responses to mitogenic stimulation. |
| 1507 | 11726533 | The vitamin D hormone stimulates transforming growth factor TGFbeta-1 and interleukin 4 (IL-4) production, which in turn may suppress inflammatory T cell activity. |
| 1508 | 11754351 | Lower expression levels in beta-cells support immune regulation resulting in induction of autoreactive, regulatory cells characterized by increased IL-4 production (Th2-like), whereas higher levels favor Th1-like autoaggressive responses characterized by augmented IFN-gamma generation. |
| 1509 | 11755473 | Although the cytokine TGF-beta is secreted from regulatory T-cells (Th3), and is related to oral tolerance, the interleukin-2 (IL-2, Th1)/IL-4 (Th2) ratio in the patient group was significantly elevated (P<0.001), which might indicate that the oral tolerance is impaired in patients. |
| 1510 | 11756326 | Previous studies using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) have demonstrated that islet xenograft rejection in mice is dominated by Th2-associated cytokines, i.e., interleukin (IL)-4 and IL-10. |
| 1511 | 11756326 | By day 1, mRNA expression levels of IL-1 beta, IL-2, IL-12p40, interferon-gamma, and tumor necrosis factor-alpha were already induced in the lymph nodes. |
| 1512 | 11757078 | NKT cells are a subset of T cells that are distinct in being able to produce cytokines such as IL-4 and IFN-gamma extremely rapidly following activation. |
| 1513 | 11781358 | We also report low numbers of resting CD4(+) CD25(+) T cells in IMD patients, a subset of T cells shown to have important immunoregulatory functions in abrogating autoimmunities in 3-day thymectomized experimental mice. |
| 1514 | 11781358 | Whereas a biased Th1 to Th2 cytokine profile has been suggested to underlie the pathogenesis of IMD in both species, we found defective production of IFN-gamma in our patients after in vitro stimulation of their PBMCs by phorbol-myristate acetate and ionomycin and both IFN-gamma and IL-4 deficiencies in V(alpha)24(+) NK T-enriched cells. |
| 1515 | 11860706 | Cytotoxic T lymphocyte antigen 4 (CTLA-4 or CD152) is a strong negative regulator of T cell activity. |
| 1516 | 11860706 | Like CD28 (a positive regulator) it binds to B7-1 and B7-2, and there is no known natural selective ligand. |
| 1517 | 11860706 | However, a single amino acid substitution in B7-1 (W88 > A; denoted B7-1wa) abrogates binding to CD28 but not to CTLA-4. |
| 1518 | 11860706 | Interferon-gamma and interleukin-4 were both depressed, arguing against a Th2 bias. |
| 1519 | 11861793 | The pancreatic levels of the Th1 cytokines interleukin (IL)-12, IL-1, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma were increased in both MLDS-induced and spontaneous NOD diabetes, an effect prevented by nicotine treatment. |
| 1520 | 11861793 | Nicotine treatment increased the pancreatic levels of the Th2 cytokines IL-4 and IL-10. |
| 1521 | 11872661 | In addition, Th1-type cells (gamma-interferon-positive and IL-2(+)) were decreased the most, and Th2-type cells (IL-4(+) and IL-10(+)) and Th3-type cells (transforming growth factor-beta1(+)) were increased the most in islet grafts of sirolimus and IL-2-treated mice. |
| 1522 | 11877486 | We report here that CD4(+) and CD4(-)CD8(-) (double negative [DN]) NKT cell subsets represent functionally distinct lineages with marked differences in their profile of cytokine secretion and pattern of expression of chemokine receptors, integrins, and NK receptors. |
| 1523 | 11877486 | CD4(+) NKT cells were the exclusive producers of interleukin (IL)-4 and IL-13 upon primary stimulation, whereas DN NKT cells had a strict Th1 profile and prominently expressed several NK lineage receptors. |
| 1524 | 11899074 | The delivery of transgenes capable of interfering with antigenic recognition and/or cell death [e.g., Fas ligand (FasL), Bcl-2, Bcl-XL] as well as imparting tolerance/immunoregulation [e.g., interleukin(IL)-4, IL-10, transforming growth factor (TGF)-beta], or cytoprotection [e.g., heme oxygenase-1 (HO-1), catalase, manganese superoxide dismutase (MnSOD)] may prevent recurrent type 1 diabetes in islet transplantation and offer a promising form of immunotherapy. |
| 1525 | 11907079 | First, they are restricted by a nonclassical MHC class I molecule, CD1d, which presents glycolipids; second, their TCR repertoire is very limited. |
| 1526 | 11907079 | After stimulation by their TCR, NKT cells rapidly release large amounts of cytokines, such as IL-4 and IFN-gamma. |
| 1527 | 11907079 | Analysis of cytokine production by NKT cells from splanchnic lymph nodes reveals that they produce at least as much IL-4 as IFN-gamma, in contrast to NKT cells from other organs (spleen, liver, and peripheral lymph nodes), which produce much more IFN-gamma than IL-4. |
| 1528 | 11907079 | First, they are restricted by a nonclassical MHC class I molecule, CD1d, which presents glycolipids; second, their TCR repertoire is very limited. |
| 1529 | 11907079 | After stimulation by their TCR, NKT cells rapidly release large amounts of cytokines, such as IL-4 and IFN-gamma. |
| 1530 | 11907079 | Analysis of cytokine production by NKT cells from splanchnic lymph nodes reveals that they produce at least as much IL-4 as IFN-gamma, in contrast to NKT cells from other organs (spleen, liver, and peripheral lymph nodes), which produce much more IFN-gamma than IL-4. |
| 1531 | 11940121 | Bone marrow cells from NOD.H-2k mice cultured in vitro with GM-CSF and IL-4 generated a reduced yield of dendritic cells when compared to bone marrow cells from B10.H-2k mice. |
| 1532 | 11940121 | This aberrant response to GM-CSF and IL-4 was unique to the NOD.H-2k background when compared to bone marrow cells from other H-2k congenic strains, and coculture experiments showed that it was cell-autonomous. |
| 1533 | 11940121 | Bone marrow cells from NOD.H-2k mice cultured in vitro with GM-CSF and IL-4 generated a reduced yield of dendritic cells when compared to bone marrow cells from B10.H-2k mice. |
| 1534 | 11940121 | This aberrant response to GM-CSF and IL-4 was unique to the NOD.H-2k background when compared to bone marrow cells from other H-2k congenic strains, and coculture experiments showed that it was cell-autonomous. |
| 1535 | 11956018 | In this paper, DC differentiation in NOD mice was investigated in vitro using bone marrow-derived progenitors (BM-DC) in the presence of GM-CSF and IL-4 or spleen-derived progenitors in the presence of GM-CSF and early acting cytokines such as Flt-3L and IL-6 (SPL-DC). |
| 1536 | 11992736 | In the direct PLNA, diclofenac also increased the percent of T cells in the PLN with activated phenotypes (CD44(high)CD62L(low) and CD44(high)CD62L(high)). |
| 1537 | 11992736 | Finally, an increase in the intracellular level of IL-4, but not INFgamma, was detected in CD4(+) PLN cells following the injection of diclofenac mixed with TNP-OVA. |
| 1538 | 11994455 | In GM-CSF/IL-4-supplemented bone marrow cultures, DC developed in significantly greater numbers from NOD than from NOR, BALB/c, and BL/6 mice. |
| 1539 | 11994455 | Likewise, DC developed in greater numbers from sorted (lineage(-)IL-7Ralpha(-)SCA-1(-)c-kit(+)) NOD myeloid progenitors in either GM-CSF/IL-4 or GM-CSF/stem cell factor (SCF)/TNF-alpha. [(3)H]TdR incorporation indicated that the increased generation of NOD DC was due to higher levels of myeloid progenitor proliferation. |
| 1540 | 11994455 | Consistent with these findings, NOD and NOR mice had increased numbers of DC in blood and thymus and NOD had an increased proportion of the putative myeloid DC (CD11c(+)CD11b(+)) subset within spleen. |
| 1541 | 11994455 | In GM-CSF/IL-4-supplemented bone marrow cultures, DC developed in significantly greater numbers from NOD than from NOR, BALB/c, and BL/6 mice. |
| 1542 | 11994455 | Likewise, DC developed in greater numbers from sorted (lineage(-)IL-7Ralpha(-)SCA-1(-)c-kit(+)) NOD myeloid progenitors in either GM-CSF/IL-4 or GM-CSF/stem cell factor (SCF)/TNF-alpha. [(3)H]TdR incorporation indicated that the increased generation of NOD DC was due to higher levels of myeloid progenitor proliferation. |
| 1543 | 11994455 | Consistent with these findings, NOD and NOR mice had increased numbers of DC in blood and thymus and NOD had an increased proportion of the putative myeloid DC (CD11c(+)CD11b(+)) subset within spleen. |
| 1544 | 11994496 | We examined the expression of IFN-gamma, a characteristic Th1 cytokine, and IL-4, a characteristic Th2 cytokine, in islet infiltrates of female and male NOD mice at various ages. |
| 1545 | 11994496 | IFN-gamma was significantly higher in young females, whereas IL-4 was higher in young males. |
| 1546 | 11994496 | CD4(+) T cells isolated from lymph nodes of female mice and activated with anti-CD3 and anti-CD28 Abs produced more IFN-gamma, but less IL-4, as compared with males. |
| 1547 | 11994496 | Treatment of CD4(+) T cells with estrogen significantly increased, whereas testosterone treatment decreased the IL-12-induced production of IFN-gamma. |
| 1548 | 11994496 | We then examined whether the change in IL-12-induced IFN-gamma production by treatment with sex hormones was due to the regulation of STAT4 activation. |
| 1549 | 11994496 | We found that estrogen treatment increased the phosphorylation of STAT4 in IL-12-stimulated T cells. |
| 1550 | 11994496 | We conclude that the increased susceptibility of female NOD mice to the development of autoimmune diabetes could be due to the enhancement of the Th1 immune response through the increase of IL-12-induced STAT4 activation by estrogen. |
| 1551 | 11994496 | We examined the expression of IFN-gamma, a characteristic Th1 cytokine, and IL-4, a characteristic Th2 cytokine, in islet infiltrates of female and male NOD mice at various ages. |
| 1552 | 11994496 | IFN-gamma was significantly higher in young females, whereas IL-4 was higher in young males. |
| 1553 | 11994496 | CD4(+) T cells isolated from lymph nodes of female mice and activated with anti-CD3 and anti-CD28 Abs produced more IFN-gamma, but less IL-4, as compared with males. |
| 1554 | 11994496 | Treatment of CD4(+) T cells with estrogen significantly increased, whereas testosterone treatment decreased the IL-12-induced production of IFN-gamma. |
| 1555 | 11994496 | We then examined whether the change in IL-12-induced IFN-gamma production by treatment with sex hormones was due to the regulation of STAT4 activation. |
| 1556 | 11994496 | We found that estrogen treatment increased the phosphorylation of STAT4 in IL-12-stimulated T cells. |
| 1557 | 11994496 | We conclude that the increased susceptibility of female NOD mice to the development of autoimmune diabetes could be due to the enhancement of the Th1 immune response through the increase of IL-12-induced STAT4 activation by estrogen. |
| 1558 | 11994496 | We examined the expression of IFN-gamma, a characteristic Th1 cytokine, and IL-4, a characteristic Th2 cytokine, in islet infiltrates of female and male NOD mice at various ages. |
| 1559 | 11994496 | IFN-gamma was significantly higher in young females, whereas IL-4 was higher in young males. |
| 1560 | 11994496 | CD4(+) T cells isolated from lymph nodes of female mice and activated with anti-CD3 and anti-CD28 Abs produced more IFN-gamma, but less IL-4, as compared with males. |
| 1561 | 11994496 | Treatment of CD4(+) T cells with estrogen significantly increased, whereas testosterone treatment decreased the IL-12-induced production of IFN-gamma. |
| 1562 | 11994496 | We then examined whether the change in IL-12-induced IFN-gamma production by treatment with sex hormones was due to the regulation of STAT4 activation. |
| 1563 | 11994496 | We found that estrogen treatment increased the phosphorylation of STAT4 in IL-12-stimulated T cells. |
| 1564 | 11994496 | We conclude that the increased susceptibility of female NOD mice to the development of autoimmune diabetes could be due to the enhancement of the Th1 immune response through the increase of IL-12-induced STAT4 activation by estrogen. |
| 1565 | 11999343 | In the nonobese diabetic (NOD) mouse, the T helper (Th)1-type inflammatory cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha play a critical role in the development of type 1 diabetes, whereas the Th2-type anti-inflammatory cytokines interleukin (IL)-4 and IL-10 operate counterregulatory. |
| 1566 | 11999343 | Therefore, we used islets to study ex vivo effects of MLD-STZ and in vitro effects of STZ on IFN-gamma, TNF-alpha, IL-4, and IL-10 on both levels of protein-producing cells and the mRNA expression, as well as the mRNA expression of the Th3-type cytokine transforming growth factor TGF-beta1. |
| 1567 | 11999343 | In islets of C57BL/6 mice of both genders MLD-STZ similarly stimulated production of IFN-gamma and TNF-alpha, but significantly reduced IL-4 and IL-10 levels in male mice only. |
| 1568 | 11999343 | Here, MLD-STZ markedly decreased the levels of IFN-gamma and TNF-alpha, but significantly increased the levels of IL-4 and IL-10. |
| 1569 | 11999343 | Moreover, MLD-STZ effects on the TGF-beta1 mRNA expression were reversed to the effects on IFN-gamma and TNF-alpha. |
| 1570 | 11999343 | In the nonobese diabetic (NOD) mouse, the T helper (Th)1-type inflammatory cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha play a critical role in the development of type 1 diabetes, whereas the Th2-type anti-inflammatory cytokines interleukin (IL)-4 and IL-10 operate counterregulatory. |
| 1571 | 11999343 | Therefore, we used islets to study ex vivo effects of MLD-STZ and in vitro effects of STZ on IFN-gamma, TNF-alpha, IL-4, and IL-10 on both levels of protein-producing cells and the mRNA expression, as well as the mRNA expression of the Th3-type cytokine transforming growth factor TGF-beta1. |
| 1572 | 11999343 | In islets of C57BL/6 mice of both genders MLD-STZ similarly stimulated production of IFN-gamma and TNF-alpha, but significantly reduced IL-4 and IL-10 levels in male mice only. |
| 1573 | 11999343 | Here, MLD-STZ markedly decreased the levels of IFN-gamma and TNF-alpha, but significantly increased the levels of IL-4 and IL-10. |
| 1574 | 11999343 | Moreover, MLD-STZ effects on the TGF-beta1 mRNA expression were reversed to the effects on IFN-gamma and TNF-alpha. |
| 1575 | 11999343 | In the nonobese diabetic (NOD) mouse, the T helper (Th)1-type inflammatory cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha play a critical role in the development of type 1 diabetes, whereas the Th2-type anti-inflammatory cytokines interleukin (IL)-4 and IL-10 operate counterregulatory. |
| 1576 | 11999343 | Therefore, we used islets to study ex vivo effects of MLD-STZ and in vitro effects of STZ on IFN-gamma, TNF-alpha, IL-4, and IL-10 on both levels of protein-producing cells and the mRNA expression, as well as the mRNA expression of the Th3-type cytokine transforming growth factor TGF-beta1. |
| 1577 | 11999343 | In islets of C57BL/6 mice of both genders MLD-STZ similarly stimulated production of IFN-gamma and TNF-alpha, but significantly reduced IL-4 and IL-10 levels in male mice only. |
| 1578 | 11999343 | Here, MLD-STZ markedly decreased the levels of IFN-gamma and TNF-alpha, but significantly increased the levels of IL-4 and IL-10. |
| 1579 | 11999343 | Moreover, MLD-STZ effects on the TGF-beta1 mRNA expression were reversed to the effects on IFN-gamma and TNF-alpha. |
| 1580 | 11999343 | In the nonobese diabetic (NOD) mouse, the T helper (Th)1-type inflammatory cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha play a critical role in the development of type 1 diabetes, whereas the Th2-type anti-inflammatory cytokines interleukin (IL)-4 and IL-10 operate counterregulatory. |
| 1581 | 11999343 | Therefore, we used islets to study ex vivo effects of MLD-STZ and in vitro effects of STZ on IFN-gamma, TNF-alpha, IL-4, and IL-10 on both levels of protein-producing cells and the mRNA expression, as well as the mRNA expression of the Th3-type cytokine transforming growth factor TGF-beta1. |
| 1582 | 11999343 | In islets of C57BL/6 mice of both genders MLD-STZ similarly stimulated production of IFN-gamma and TNF-alpha, but significantly reduced IL-4 and IL-10 levels in male mice only. |
| 1583 | 11999343 | Here, MLD-STZ markedly decreased the levels of IFN-gamma and TNF-alpha, but significantly increased the levels of IL-4 and IL-10. |
| 1584 | 11999343 | Moreover, MLD-STZ effects on the TGF-beta1 mRNA expression were reversed to the effects on IFN-gamma and TNF-alpha. |
| 1585 | 12021086 | Natural killer T (NKT) cells, which comprise a minor subpopulation of T cells, play a critical role in immunoregulation as a result of a rapid burst of IL-4 and IFN-gamma secretion. |
| 1586 | 12021086 | Alpha-galactosylceramide (alpha-GalCer) specifically binds to NKT cells in a CD1-dependent manner and stimulates these cells to proliferate and to produce various cytokines, including IFN-gamma, IL-4, and IL-10. |
| 1587 | 12021086 | This protection is associated with elevated IL-4 and IL-10 in the spleen and pancreas of protected female NOD mice. |
| 1588 | 12021086 | Natural killer T (NKT) cells, which comprise a minor subpopulation of T cells, play a critical role in immunoregulation as a result of a rapid burst of IL-4 and IFN-gamma secretion. |
| 1589 | 12021086 | Alpha-galactosylceramide (alpha-GalCer) specifically binds to NKT cells in a CD1-dependent manner and stimulates these cells to proliferate and to produce various cytokines, including IFN-gamma, IL-4, and IL-10. |
| 1590 | 12021086 | This protection is associated with elevated IL-4 and IL-10 in the spleen and pancreas of protected female NOD mice. |
| 1591 | 12021086 | Natural killer T (NKT) cells, which comprise a minor subpopulation of T cells, play a critical role in immunoregulation as a result of a rapid burst of IL-4 and IFN-gamma secretion. |
| 1592 | 12021086 | Alpha-galactosylceramide (alpha-GalCer) specifically binds to NKT cells in a CD1-dependent manner and stimulates these cells to proliferate and to produce various cytokines, including IFN-gamma, IL-4, and IL-10. |
| 1593 | 12021086 | This protection is associated with elevated IL-4 and IL-10 in the spleen and pancreas of protected female NOD mice. |
| 1594 | 12021108 | Cytokine secretion (TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, and IL-10) was measured in the supernatants of the cultures stimulated with 21 overlapping preproinsulin peptides as well as proinsulin and insulin. |
| 1595 | 12021108 | In Ab+ individuals our results reveal higher IL-4 levels in CD45RO+ memory cells and higher IL-5 levels in CD45RA+ naive/resting cells, while higher IL-2 production was found in PBMCs. |
| 1596 | 12021108 | In contrast, in PBMCs of T1D patients higher IFN-gamma and IL-10 secretion was found. |
| 1597 | 12021108 | Cytokine secretion (TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, and IL-10) was measured in the supernatants of the cultures stimulated with 21 overlapping preproinsulin peptides as well as proinsulin and insulin. |
| 1598 | 12021108 | In Ab+ individuals our results reveal higher IL-4 levels in CD45RO+ memory cells and higher IL-5 levels in CD45RA+ naive/resting cells, while higher IL-2 production was found in PBMCs. |
| 1599 | 12021108 | In contrast, in PBMCs of T1D patients higher IFN-gamma and IL-10 secretion was found. |
| 1600 | 12086941 | Continuous addition of TX527 impaired interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF)-driven DC differentiation as well as lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-induced maturation into Th1-promoting DC (DC1), as characterized by marked changes in DC morphology and abrogation of IL-12p70 release upon CD40 ligation. |
| 1601 | 12086941 | Continuously TX527-treated DCs significantly inhibited T-cell proliferation and blocked IFN-gamma, IL-10, but not IL-13 production, whereas DCs treated during maturation failed to inhibit T-cell proliferation but affected IL-10 and IFN-gamma production. |
| 1602 | 12086942 | Immunological characterization and therapeutic activity of an altered-peptide ligand, NBI-6024, based on the immunodominant type 1 diabetes autoantigen insulin B-chain (9-23) peptide. |
| 1603 | 12086942 | However, vaccinations with the APLs induced strong cellular responses, as measured by in vitro lymphocyte proliferation and Th2 cytokine production (i.e., interleukin [IL]-4 and IL-10, but not gamma-interferon [IFN-gamma]). |
| 1604 | 12115623 | We previously demonstrated that immunotherapy with dendritic cells (DC) prevented diabetes development in prediabetic NOD mice and that this effect was optimal when using a stimulatory DC population generated from bone marrow cells cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. |
| 1605 | 12115623 | In this study, we have investigated the mechanism by which GM-CSF- and IL-4-cultured DC prevent diabetes in prediabetic NOD mice. |
| 1606 | 12115623 | Furthermore, sorted CD45RB(lo) CD25+ CD4+ T cells from the spleen of DC-treated mice produced high amounts of Th2 cytokines following anti-TCR stimulation, suggesting that these cells are responsible for the apparent Th2 shift. |
| 1607 | 12115623 | We previously demonstrated that immunotherapy with dendritic cells (DC) prevented diabetes development in prediabetic NOD mice and that this effect was optimal when using a stimulatory DC population generated from bone marrow cells cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. |
| 1608 | 12115623 | In this study, we have investigated the mechanism by which GM-CSF- and IL-4-cultured DC prevent diabetes in prediabetic NOD mice. |
| 1609 | 12115623 | Furthermore, sorted CD45RB(lo) CD25+ CD4+ T cells from the spleen of DC-treated mice produced high amounts of Th2 cytokines following anti-TCR stimulation, suggesting that these cells are responsible for the apparent Th2 shift. |
| 1610 | 12145160 | Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 healthy control subjects were examined for expression of the chemokine receptors CXCR4 (naive T-cells), CCR5 and CXCR3 (Th1 associated), and CCR3 and CCR4 (Th2 associated) on CD3+ lymphocytes. |
| 1611 | 12145160 | Furthermore, we analyzed chemokine serum levels (monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and RANTES [regulated on activation, normal T-cell expressed and secreted]) and phytohemagglutinin (PHA)-stimulated cytokine secretion of Th1- (gamma-interferon [IFN-gamma] and tumor necrosis factor-alpha [TNF-alpha]) and Th2 (interleukin [IL]-4 and -10)-associated cytokines by PBMC. |
| 1612 | 12145160 | The PBMCs of patients with newly diagnosed but not with longstanding type 1 diabetes showed reduced expression of the Th1-associated chemokine receptors CCR5 (P < 0.001 vs. control subjects) and CXCR3 (P < 0.002 vs. control subjects). |
| 1613 | 12145160 | This reduction correlated with reduced IFN-gamma and TNF-alpha production of PBMCs after PHA stimulation and reversed 6-12 months after diagnosis to normal levels. |
| 1614 | 12145160 | CCR4 cells were reduced in both newly diagnosed and longstanding type 1 diabetic patients, which correlated to reduced PHA-stimulated IL-4 production. |
| 1615 | 12145160 | MIP-1alpha and MIP-1beta levels were considerably elevated in a subgroup of patients with newly diagnosed diabetes. |
| 1616 | 12145160 | Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 healthy control subjects were examined for expression of the chemokine receptors CXCR4 (naive T-cells), CCR5 and CXCR3 (Th1 associated), and CCR3 and CCR4 (Th2 associated) on CD3+ lymphocytes. |
| 1617 | 12145160 | Furthermore, we analyzed chemokine serum levels (monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and RANTES [regulated on activation, normal T-cell expressed and secreted]) and phytohemagglutinin (PHA)-stimulated cytokine secretion of Th1- (gamma-interferon [IFN-gamma] and tumor necrosis factor-alpha [TNF-alpha]) and Th2 (interleukin [IL]-4 and -10)-associated cytokines by PBMC. |
| 1618 | 12145160 | The PBMCs of patients with newly diagnosed but not with longstanding type 1 diabetes showed reduced expression of the Th1-associated chemokine receptors CCR5 (P < 0.001 vs. control subjects) and CXCR3 (P < 0.002 vs. control subjects). |
| 1619 | 12145160 | This reduction correlated with reduced IFN-gamma and TNF-alpha production of PBMCs after PHA stimulation and reversed 6-12 months after diagnosis to normal levels. |
| 1620 | 12145160 | CCR4 cells were reduced in both newly diagnosed and longstanding type 1 diabetic patients, which correlated to reduced PHA-stimulated IL-4 production. |
| 1621 | 12145160 | MIP-1alpha and MIP-1beta levels were considerably elevated in a subgroup of patients with newly diagnosed diabetes. |
| 1622 | 12145162 | CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4(+) T helper 1 (Th1) cells. |
| 1623 | 12145162 | In CCR5(-/-) mice, intragraft mRNA expression of interleukin-4 and -5 was increased, whereas that of interferon-gamma was decreased, corresponding to a Th2 pattern of T-cell activation in the target tissues compared with a Th1 pattern observed in controls. |
| 1624 | 12165974 | The IL-4R alpha chain acts as the high affinity binding chain and the principal signaling chain for IL-4; it also acts as the signaling chain for IL-13, but in this case the IL-13R alpha 1 chain conveys the bulk of the cytokine specificity. |
| 1625 | 12165974 | Thus, IL-4R alpha knock-out mice are unresponsive to both IL-4 and IL-13. |
| 1626 | 12165974 | The finding that the lack of IL-4R alpha chain protects TCR-HA, INS-HA double transgenic mice against diabetes, and death implies that either IL-4 or IL-13 plays a role in the progression of this disease. |
| 1627 | 12165974 | The IL-4R alpha chain acts as the high affinity binding chain and the principal signaling chain for IL-4; it also acts as the signaling chain for IL-13, but in this case the IL-13R alpha 1 chain conveys the bulk of the cytokine specificity. |
| 1628 | 12165974 | Thus, IL-4R alpha knock-out mice are unresponsive to both IL-4 and IL-13. |
| 1629 | 12165974 | The finding that the lack of IL-4R alpha chain protects TCR-HA, INS-HA double transgenic mice against diabetes, and death implies that either IL-4 or IL-13 plays a role in the progression of this disease. |
| 1630 | 12165974 | The IL-4R alpha chain acts as the high affinity binding chain and the principal signaling chain for IL-4; it also acts as the signaling chain for IL-13, but in this case the IL-13R alpha 1 chain conveys the bulk of the cytokine specificity. |
| 1631 | 12165974 | Thus, IL-4R alpha knock-out mice are unresponsive to both IL-4 and IL-13. |
| 1632 | 12165974 | The finding that the lack of IL-4R alpha chain protects TCR-HA, INS-HA double transgenic mice against diabetes, and death implies that either IL-4 or IL-13 plays a role in the progression of this disease. |
| 1633 | 12182467 | Benign insulitis with macrophages, B cells, CD4 > CD8 T cells and low levels of IL-2R, IL-2, IFN-gamma and IL-4 was seen in islets from the native pancreas and in long surviving pancreas isografts in mice that remained in remission. |
| 1634 | 12182843 | Supernatants from cultured splenocytes and peritoneal cells taken from Linomide-treated mice contained lower levels of TNFalpha, IL-1 beta, IFN gamma and IL-12 versus higher levels of IL-4, IL-6 and IL-10 in comparison with supernatants from cultures of untreated mice. |
| 1635 | 12210732 | These effects are completely counteracted by the administration of IL-4, a Th2 protective cytokine; IL-10, another putative Th2 cytokine, exerts direct effects upon endothelial cell (EC) function, as shown by the increase of endothelial nitric oxide synthase (eNOS) mRNA transcripts and by the release of endothelial NO which, in turn, exert vasodilatory effects; moreover, this cytokine significantly upregulates adhesion molecules on endothelia. |
| 1636 | 12210732 | On the other hand, IL-1beta, a Th1 proinflammatory cytokine, dramatically increases nitrite and nitrate levels, as well as inducible nitric oxide synthase (iNOS) transcripts and also upregulates islet ICAM-1 expression as well as circulating ICAM-1 levels. |
| 1637 | 12235110 | Defects in IL-4-producing CD1d-autoreactive NKT cells have been implicated in numerous Th1-mediated autoimmune diseases, including diabetes, multiple sclerosis, rheumatoid arthritis, lupus, and systemic sclerosis. |
| 1638 | 12235110 | Particular attention has been focused on autoimmune insulin-dependent diabetes mellitus (IDDM) because nonobese diabetic (NOD) mice and humans with IDDM are both reported to express severe deficiencies in the frequency and Th2 functions of NKT cells. |
| 1639 | 12235110 | We have now devised a direct, highly specific CD1d tetramer-based methodology to test whether humans with IDDM have associated NKT cell defects. |
| 1640 | 12235110 | Surprisingly, although we find marked and stable differences in NKT cells between individuals, our study of IDDM patients and healthy controls, including discordant twin pairs, demonstrates that NKT cell frequency and IL-4 production are conserved during the course of IDDM. |
| 1641 | 12235110 | Defects in IL-4-producing CD1d-autoreactive NKT cells have been implicated in numerous Th1-mediated autoimmune diseases, including diabetes, multiple sclerosis, rheumatoid arthritis, lupus, and systemic sclerosis. |
| 1642 | 12235110 | Particular attention has been focused on autoimmune insulin-dependent diabetes mellitus (IDDM) because nonobese diabetic (NOD) mice and humans with IDDM are both reported to express severe deficiencies in the frequency and Th2 functions of NKT cells. |
| 1643 | 12235110 | We have now devised a direct, highly specific CD1d tetramer-based methodology to test whether humans with IDDM have associated NKT cell defects. |
| 1644 | 12235110 | Surprisingly, although we find marked and stable differences in NKT cells between individuals, our study of IDDM patients and healthy controls, including discordant twin pairs, demonstrates that NKT cell frequency and IL-4 production are conserved during the course of IDDM. |
| 1645 | 12369724 | Current evidence indicates that islet beta cell-specific autoreactive T cells belong to a T helper 1 (Th1) subset, and these Th1 cells and their characteristic cytokine products, IFNgamma and IL-2, are believed to cause islet inflammation (insulitis) and beta cell destruction. |
| 1646 | 12369724 | Approaches that attempt to correct underlying immunoregulatory defects in autoimmune diabetes include interventions aimed at i) deleting beta cell autoreactive Th1 cells and cytokines (IFNgamma and IL-2) and/or ii) increasing regulatory Th2 cells and/or Th3 cells and their cytokine products (IL-4, IL-10 and TGFbeta1). |
| 1647 | 12390307 | Protection induced by CTB-insulin was transferred to naive recipients by splenic CD4+ T cells. |
| 1648 | 12390307 | Reverse transcription-polymerase chain reaction analysis of recipients' pancreatic glands revealed an increase of TGF-beta and IL-10 transcripts after donor mice tolerization, while levels of IFN-gamma and IL-4 RNAs were unchanged. |
| 1649 | 12390307 | Higher amounts of IL-4 and IFN-gamma were noticed in pancreatic lymph nodes of tolerized mice upon in vitro stimulation. |
| 1650 | 12390307 | Protection induced by CTB-insulin was transferred to naive recipients by splenic CD4+ T cells. |
| 1651 | 12390307 | Reverse transcription-polymerase chain reaction analysis of recipients' pancreatic glands revealed an increase of TGF-beta and IL-10 transcripts after donor mice tolerization, while levels of IFN-gamma and IL-4 RNAs were unchanged. |
| 1652 | 12390307 | Higher amounts of IL-4 and IFN-gamma were noticed in pancreatic lymph nodes of tolerized mice upon in vitro stimulation. |
| 1653 | 12401728 | IL4R encodes a subunit of the interleukin-4 receptor, a molecule critical to T-helper cell development. |
| 1654 | 12401728 | In particular, we have identified a specific haplotype that appears to be protective and observed that this protective effect is strongest among individuals not carrying the HLA DR3/DR4 genotype (which confers the strongest genetic risk for type 1 diabetes). |
| 1655 | 12430864 | NKT rapidly releases IL-4 and IFN-gamma at high level when activated. |
| 1656 | 12438968 | The failure of IL-4 expressing islets was not associated with cellular toxicity of rAAV or impairment of glucose-stimulated insulin release in vitro. |
| 1657 | 12439784 | IL-4-Ig was found to downregulate LPS-induced IFN-gamma and TNF-alpha production. |
| 1658 | 12439784 | Expression was downregulated for both Th1-specific cytokine IFN-gamma and the Th2-specific cytokine IL-10. |
| 1659 | 12439784 | Interestingly, infiltration increased in the islets of IL-4-Ig-treated animals, and therefore did not correlate with the decreased IFN-gamma expression. |
| 1660 | 12439784 | IL-4-Ig was found to downregulate LPS-induced IFN-gamma and TNF-alpha production. |
| 1661 | 12439784 | Expression was downregulated for both Th1-specific cytokine IFN-gamma and the Th2-specific cytokine IL-10. |
| 1662 | 12439784 | Interestingly, infiltration increased in the islets of IL-4-Ig-treated animals, and therefore did not correlate with the decreased IFN-gamma expression. |
| 1663 | 12444170 | Increased nonobese diabetic Th1:Th2 (IFN-gamma:IL-4) ratio is CD4+ T cell intrinsic and independent of APC genetic background. |
| 1664 | 12444170 | In this study, we demonstrate that increased IFN-gamma, decreased IL-4, and decreased IL-10 production in NOD T cells is CD4 T cell intrinsic. |
| 1665 | 12444170 | NOD CD4(+) T cells purified and stimulated with anti-CD3/anti-CD28 Abs generated greater IFN-gamma, less IL-4, and less IL-10 than B6.G7 CD4(+) T cells. |
| 1666 | 12444170 | Moreover, the increased IFN-gamma:IL-4 cytokine ratio was independent of the genetic background of APCs, since NOD CD4(+) T cells generated increased IFN-gamma and decreased IL-4 compared with B6.G7 CD4(+) T cells, regardless of whether they were stimulated with NOD or B6.G7 APCs. |
| 1667 | 12444170 | Cell cycle analysis showed that the cytokine differences were not due to cycle/proliferative differences between NOD and B6.G7, since stimulated CD4(+) T cells from both strains showed quantitatively identical entry into subsequent cell divisions (shown by CFSE staining), although NOD cells showed greater numbers of IFN-gamma-positive cells with each subsequent cell division. |
| 1668 | 12444170 | Moreover, 7-aminoactinomycin D and 5-bromo-2'-deoxyuridine analysis showed indistinguishable entry into G(0)/G(1), S, and G(2)/M phases of the cell cycle for both NOD and B6.G7 CD4(+) cells, with both strains generating IFN-gamma predominantly in the S phase. |
| 1669 | 12444170 | Increased nonobese diabetic Th1:Th2 (IFN-gamma:IL-4) ratio is CD4+ T cell intrinsic and independent of APC genetic background. |
| 1670 | 12444170 | In this study, we demonstrate that increased IFN-gamma, decreased IL-4, and decreased IL-10 production in NOD T cells is CD4 T cell intrinsic. |
| 1671 | 12444170 | NOD CD4(+) T cells purified and stimulated with anti-CD3/anti-CD28 Abs generated greater IFN-gamma, less IL-4, and less IL-10 than B6.G7 CD4(+) T cells. |
| 1672 | 12444170 | Moreover, the increased IFN-gamma:IL-4 cytokine ratio was independent of the genetic background of APCs, since NOD CD4(+) T cells generated increased IFN-gamma and decreased IL-4 compared with B6.G7 CD4(+) T cells, regardless of whether they were stimulated with NOD or B6.G7 APCs. |
| 1673 | 12444170 | Cell cycle analysis showed that the cytokine differences were not due to cycle/proliferative differences between NOD and B6.G7, since stimulated CD4(+) T cells from both strains showed quantitatively identical entry into subsequent cell divisions (shown by CFSE staining), although NOD cells showed greater numbers of IFN-gamma-positive cells with each subsequent cell division. |
| 1674 | 12444170 | Moreover, 7-aminoactinomycin D and 5-bromo-2'-deoxyuridine analysis showed indistinguishable entry into G(0)/G(1), S, and G(2)/M phases of the cell cycle for both NOD and B6.G7 CD4(+) cells, with both strains generating IFN-gamma predominantly in the S phase. |
| 1675 | 12444170 | Increased nonobese diabetic Th1:Th2 (IFN-gamma:IL-4) ratio is CD4+ T cell intrinsic and independent of APC genetic background. |
| 1676 | 12444170 | In this study, we demonstrate that increased IFN-gamma, decreased IL-4, and decreased IL-10 production in NOD T cells is CD4 T cell intrinsic. |
| 1677 | 12444170 | NOD CD4(+) T cells purified and stimulated with anti-CD3/anti-CD28 Abs generated greater IFN-gamma, less IL-4, and less IL-10 than B6.G7 CD4(+) T cells. |
| 1678 | 12444170 | Moreover, the increased IFN-gamma:IL-4 cytokine ratio was independent of the genetic background of APCs, since NOD CD4(+) T cells generated increased IFN-gamma and decreased IL-4 compared with B6.G7 CD4(+) T cells, regardless of whether they were stimulated with NOD or B6.G7 APCs. |
| 1679 | 12444170 | Cell cycle analysis showed that the cytokine differences were not due to cycle/proliferative differences between NOD and B6.G7, since stimulated CD4(+) T cells from both strains showed quantitatively identical entry into subsequent cell divisions (shown by CFSE staining), although NOD cells showed greater numbers of IFN-gamma-positive cells with each subsequent cell division. |
| 1680 | 12444170 | Moreover, 7-aminoactinomycin D and 5-bromo-2'-deoxyuridine analysis showed indistinguishable entry into G(0)/G(1), S, and G(2)/M phases of the cell cycle for both NOD and B6.G7 CD4(+) cells, with both strains generating IFN-gamma predominantly in the S phase. |
| 1681 | 12444170 | Increased nonobese diabetic Th1:Th2 (IFN-gamma:IL-4) ratio is CD4+ T cell intrinsic and independent of APC genetic background. |
| 1682 | 12444170 | In this study, we demonstrate that increased IFN-gamma, decreased IL-4, and decreased IL-10 production in NOD T cells is CD4 T cell intrinsic. |
| 1683 | 12444170 | NOD CD4(+) T cells purified and stimulated with anti-CD3/anti-CD28 Abs generated greater IFN-gamma, less IL-4, and less IL-10 than B6.G7 CD4(+) T cells. |
| 1684 | 12444170 | Moreover, the increased IFN-gamma:IL-4 cytokine ratio was independent of the genetic background of APCs, since NOD CD4(+) T cells generated increased IFN-gamma and decreased IL-4 compared with B6.G7 CD4(+) T cells, regardless of whether they were stimulated with NOD or B6.G7 APCs. |
| 1685 | 12444170 | Cell cycle analysis showed that the cytokine differences were not due to cycle/proliferative differences between NOD and B6.G7, since stimulated CD4(+) T cells from both strains showed quantitatively identical entry into subsequent cell divisions (shown by CFSE staining), although NOD cells showed greater numbers of IFN-gamma-positive cells with each subsequent cell division. |
| 1686 | 12444170 | Moreover, 7-aminoactinomycin D and 5-bromo-2'-deoxyuridine analysis showed indistinguishable entry into G(0)/G(1), S, and G(2)/M phases of the cell cycle for both NOD and B6.G7 CD4(+) cells, with both strains generating IFN-gamma predominantly in the S phase. |
| 1687 | 12473243 | Purified CD62L+CD4+ cells from CTB-insulin fed mice significantly reduced the capacity of diabetogenic T cells to transfer diabetes in syngeneic recipients. |
| 1688 | 12473243 | In vitro stimulated CD62L+CD4+ cells from the spleen of fed animals secreted lower amounts of IL-4 and IL-10 but comparable levels of TGFbeta than CD62L-cells. |
| 1689 | 12473243 | A reduced IFN-gamma production between the two cell subsets was specifically observed in CTB-insulin fed mice. |
| 1690 | 12473243 | Taken together, our results suggest that L-selectin and alpha4-integrin have distinct but complementary roles in the generation and function of regulatory CD4+ T cells following CTB-insulin administration. |
| 1691 | 12500188 | These observations were further confirmed by the results of CD4(+) enzyme-linked immunospot assay for interferon (IFN)-gamma and interleukin (IL)-4 and intracellular cytokine staining of IFN-gamma producing CD8(+) cells. |
| 1692 | 12502802 | A comparison of the frequency of gamma interferon (IFN-gamma)-producing CD4(+) and CD8(+) T cells in peripheral blood by ELISpot assay did not reveal any correlation between viral clearance and T-cell responses. |
| 1693 | 12502802 | In addition, analyses of IFN-gamma, IFN-alpha, and interleukin-4 mRNA levels in liver biopsies, presumably indicative of intrahepatic T-cell responses, revealed no distinct pattern in these chimpanzees with respect to infection outcome. |
| 1694 | 12570678 | In particular, we have successfully used this approach to deliver neutralizing cytokine receptors such as interferon gamma (IFNgamma)-receptor-Ig fusion proteins or anti-inflammatory cytokines such as transforming growth factor beta-1 (TGF-beta1) and interleukin 4 (IL-4). |
| 1695 | 12570678 | Intramuscular gene therapy is effective in protecting against several experimental autoimmune diseases including insulin-dependent diabetes mellitus (IDDM), experimental allergic encephalomyelitis (EAE), and systemic lupus erythematosus (SLE). |
| 1696 | 12570826 | Most notably, repeated administration of alpha-GalCer to mice favors the generation of conventional T lymphocytes producing T helper (Th) type 2 cytokines such as IL-4 and IL-10. |
| 1697 | 12573055 | DC infected with any of the Ad vectors expressed higher levels of CD40, CD80, and CD86 molecules than uninfected DC and Ad.IL-4 DC produced IL-4 after lipopolysaccharide (LPS) and interferon (IFN)-gamma stimulation. |
| 1698 | 12573055 | Ad-infected DC efficiently stimulated allogeneic T cells, and cultures of T cells with Ad.IL-4 DC produced lower levels of IFN-gamma and marginally higher levels of IL-4. |
| 1699 | 12573055 | The intrapancreatic IFN-gamma:IL-4 or IFN-gamma:IL-10 cytokine ratios were lower in 10-week-old mice treated with Ad.IL-4 DC, and these mice were significantly protected from disease. |
| 1700 | 12573055 | DC infected with any of the Ad vectors expressed higher levels of CD40, CD80, and CD86 molecules than uninfected DC and Ad.IL-4 DC produced IL-4 after lipopolysaccharide (LPS) and interferon (IFN)-gamma stimulation. |
| 1701 | 12573055 | Ad-infected DC efficiently stimulated allogeneic T cells, and cultures of T cells with Ad.IL-4 DC produced lower levels of IFN-gamma and marginally higher levels of IL-4. |
| 1702 | 12573055 | The intrapancreatic IFN-gamma:IL-4 or IFN-gamma:IL-10 cytokine ratios were lower in 10-week-old mice treated with Ad.IL-4 DC, and these mice were significantly protected from disease. |
| 1703 | 12573055 | DC infected with any of the Ad vectors expressed higher levels of CD40, CD80, and CD86 molecules than uninfected DC and Ad.IL-4 DC produced IL-4 after lipopolysaccharide (LPS) and interferon (IFN)-gamma stimulation. |
| 1704 | 12573055 | Ad-infected DC efficiently stimulated allogeneic T cells, and cultures of T cells with Ad.IL-4 DC produced lower levels of IFN-gamma and marginally higher levels of IL-4. |
| 1705 | 12573055 | The intrapancreatic IFN-gamma:IL-4 or IFN-gamma:IL-10 cytokine ratios were lower in 10-week-old mice treated with Ad.IL-4 DC, and these mice were significantly protected from disease. |
| 1706 | 12574327 | We show that a Th1 (IFN-gamma) pancreatic environment greatly accelerates the recruitment of adoptively transferred islet-specific CD4 T cells to the islets and also accelerates the onset of diabetes. |
| 1707 | 12574327 | Increased recruitment to the islets was also observed in the presence of IL-4, but to a lesser extent than in the presence of IFN-gamma, and this lesser increase in the rate of recruitment did not accelerate diabetes onset within the time period examined. |
| 1708 | 12594256 | HSP60 strongly stimulated DC for maturation and release of TNF-alpha, IL-12, and IL-1 beta. |
| 1709 | 12594256 | However, HSP60 elicited only a weak IL-10 response in DC suggesting a Th1 bias. |
| 1710 | 12594256 | Again, a Th1 bias was noted in that cocultures of allogeneic T cells and HSP60-treated DC released IFN-gamma but only small amounts of IL-10 and no detectable IL-4. |
| 1711 | 12594256 | Signaling via Toll-like receptor 4 was involved in HSP60-induced cytokine release and maturation because DC of C3H/HeJ mice with a mutant Toll-like receptor 4 showed deficient response to HSP60. |
| 1712 | 12594256 | HSP60 was found to rapidly activate the mitogen-activated protein kinases p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase as well as I kappa B in DC. |
| 1713 | 12594305 | Skewing their cytokine production from a Th1 (primarily IFN-gamma) to a Th2 (primarily IL-4 and IL-10) pattern is a widely proposed approach to dampen the pathogenicity of autoreactive diabetogenic T cells. |
| 1714 | 12594305 | Murine CD4 T cells are characterized by a reciprocal relationship between the production of IFN-gamma and expression of the beta-chain component of its receptor (IFN-gamma RB). |
| 1715 | 12594305 | Thus, NOD mice constitutively expressing a CD2 promoter-driven IFN-gamma RB transgene in all T cells are Th1-deficient. |
| 1716 | 12594852 | The imbalance of Th1/Th2 subsets is an important pathogenic mechanism for insulin-dependent diabetes mellitus (IDDM). |
| 1717 | 12594852 | We hypothesize that exogenous CGRP administration during insulitis may modulate the balance of Th lymphocytes, thereby providing a therapeutic intervention for IDDM. |
| 1718 | 12594852 | The effect of CGRP gene transfer on pathogenesis of IDDM was observedin autoimmune diabetic C57BL mice induced by multiple low-dose streptozotocin (MLDS) administration. |
| 1719 | 12594852 | CGRP gene transfer significantly inhibited T cell proliferation and secretion of the Th1 cytokine IFN-gamma, increased the level of the Th2 cytokine IL-10, but had no effect on IL-4 and TGF-beta1 secretion. |
| 1720 | 12594852 | CGRP gene transfer also decreased IL-12 and IFN-gamma levels in peritoneal effusion. |
| 1721 | 12594852 | Our results demonstrate that CGRP gene transfer selectively suppresses the pro-inflammatory Th1 subsets and promote anti-inflammatory Th2 subsets, resulting in amelioration of beta cell destruction and reduction of IDDM occurrence in mice with MLDS-induced diabetes. |
| 1722 | 12628339 | Prevention of autoimmune insulitis by delivery of a chimeric plasmid encoding interleukin-4 and interleukin-10. |
| 1723 | 12628339 | The combined administration of interleukin-4 (IL-4) and interleukin-10 (IL-10) expression plasmids has demonstrated synergistic effects on the prevention of autoimmune diabetes. |
| 1724 | 12628339 | To this end, we constructed a co-expression 'chimeric' plasmid, pCMV-IL4-IL10, in which the expression of IL-4 and IL-10 was driven by two separate CMV immediate early promoters by using the biodegradable polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) as a gene carrier to optimize gene delivery. |
| 1725 | 12628339 | While both groups had persistent gene expression longer than 5 weeks, the IL-4 and IL-10 serum levels of the chimeric group were higher than those in the co-administration group. |
| 1726 | 12628339 | These results suggest that the chimeric IL-4 and IL-10 expression plasmid can effectively reduce the incidence of autoimmune insulitis. |
| 1727 | 12628339 | Prevention of autoimmune insulitis by delivery of a chimeric plasmid encoding interleukin-4 and interleukin-10. |
| 1728 | 12628339 | The combined administration of interleukin-4 (IL-4) and interleukin-10 (IL-10) expression plasmids has demonstrated synergistic effects on the prevention of autoimmune diabetes. |
| 1729 | 12628339 | To this end, we constructed a co-expression 'chimeric' plasmid, pCMV-IL4-IL10, in which the expression of IL-4 and IL-10 was driven by two separate CMV immediate early promoters by using the biodegradable polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) as a gene carrier to optimize gene delivery. |
| 1730 | 12628339 | While both groups had persistent gene expression longer than 5 weeks, the IL-4 and IL-10 serum levels of the chimeric group were higher than those in the co-administration group. |
| 1731 | 12628339 | These results suggest that the chimeric IL-4 and IL-10 expression plasmid can effectively reduce the incidence of autoimmune insulitis. |
| 1732 | 12628339 | Prevention of autoimmune insulitis by delivery of a chimeric plasmid encoding interleukin-4 and interleukin-10. |
| 1733 | 12628339 | The combined administration of interleukin-4 (IL-4) and interleukin-10 (IL-10) expression plasmids has demonstrated synergistic effects on the prevention of autoimmune diabetes. |
| 1734 | 12628339 | To this end, we constructed a co-expression 'chimeric' plasmid, pCMV-IL4-IL10, in which the expression of IL-4 and IL-10 was driven by two separate CMV immediate early promoters by using the biodegradable polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) as a gene carrier to optimize gene delivery. |
| 1735 | 12628339 | While both groups had persistent gene expression longer than 5 weeks, the IL-4 and IL-10 serum levels of the chimeric group were higher than those in the co-administration group. |
| 1736 | 12628339 | These results suggest that the chimeric IL-4 and IL-10 expression plasmid can effectively reduce the incidence of autoimmune insulitis. |
| 1737 | 12628339 | Prevention of autoimmune insulitis by delivery of a chimeric plasmid encoding interleukin-4 and interleukin-10. |
| 1738 | 12628339 | The combined administration of interleukin-4 (IL-4) and interleukin-10 (IL-10) expression plasmids has demonstrated synergistic effects on the prevention of autoimmune diabetes. |
| 1739 | 12628339 | To this end, we constructed a co-expression 'chimeric' plasmid, pCMV-IL4-IL10, in which the expression of IL-4 and IL-10 was driven by two separate CMV immediate early promoters by using the biodegradable polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) as a gene carrier to optimize gene delivery. |
| 1740 | 12628339 | While both groups had persistent gene expression longer than 5 weeks, the IL-4 and IL-10 serum levels of the chimeric group were higher than those in the co-administration group. |
| 1741 | 12628339 | These results suggest that the chimeric IL-4 and IL-10 expression plasmid can effectively reduce the incidence of autoimmune insulitis. |
| 1742 | 12628339 | Prevention of autoimmune insulitis by delivery of a chimeric plasmid encoding interleukin-4 and interleukin-10. |
| 1743 | 12628339 | The combined administration of interleukin-4 (IL-4) and interleukin-10 (IL-10) expression plasmids has demonstrated synergistic effects on the prevention of autoimmune diabetes. |
| 1744 | 12628339 | To this end, we constructed a co-expression 'chimeric' plasmid, pCMV-IL4-IL10, in which the expression of IL-4 and IL-10 was driven by two separate CMV immediate early promoters by using the biodegradable polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) as a gene carrier to optimize gene delivery. |
| 1745 | 12628339 | While both groups had persistent gene expression longer than 5 weeks, the IL-4 and IL-10 serum levels of the chimeric group were higher than those in the co-administration group. |
| 1746 | 12628339 | These results suggest that the chimeric IL-4 and IL-10 expression plasmid can effectively reduce the incidence of autoimmune insulitis. |
| 1747 | 12653847 | Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis. |
| 1748 | 12653847 | We tested for both binding and neutralizing autoantibodies to a range of human cytokines, including interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, interferon-alpha2 (IFN-alpha2), IFN-omega, IFN-beta, IFN-gamma, tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta1) and granulocyte-macrophage colony stimulating factor (GM-CSF), in plasmas or sera. |
| 1749 | 12653847 | With two notable exceptions described below, we found only occasional, mostly low-titre, non-neutralizing antibodies, mainly to GM-CSF; also to IL-10 in pemphigoid. |
| 1750 | 12653847 | Strikingly, however, high-titre, mainly IgG, autoantibodies to IFN-alpha2, IFN-omega and IL-12 were common at diagnosis in patients with late-onset myasthenia gravis (LOMG+), thymoma (T) but no MG (TMG-) and especially with both thymoma and MG together (TMG+). |
| 1751 | 12653847 | The antibodies recognized other closely related type I IFN-alpha subtypes, but rarely the distantly related type I IFN-beta, and never (detectably) the unrelated type II IFN-gamma. |
| 1752 | 12653847 | Antibodies to IL-12 showed a similar distribution to those against IFN-alpha2, although prevalences were slightly lower; correlations between individual titres against each were so modest that they appear to be entirely different specificities. |
| 1753 | 12657834 | A short-term administration of antibodies against ICAM-1/LFA-1 or CD8 molecules during a critical period of younger age resulted in complete protection of autoimmune diabetes in NOD mice. |
| 1754 | 12657834 | Furthermore, semiquantitative RT-PCR analysis of cytokines showed that T cells from anti-CD8-treated mice could express IFN-gamma, IL-4, IL-10 and TGF-beta1 in response to islet antigen. |
| 1755 | 12657834 | In contrast, T cells from anti-ICAM-1/LFA-1-treated mice expressed IFN-gamma, IL-10 and TGF-beta1 but not IL-4. |
| 1756 | 12657834 | A short-term administration of antibodies against ICAM-1/LFA-1 or CD8 molecules during a critical period of younger age resulted in complete protection of autoimmune diabetes in NOD mice. |
| 1757 | 12657834 | Furthermore, semiquantitative RT-PCR analysis of cytokines showed that T cells from anti-CD8-treated mice could express IFN-gamma, IL-4, IL-10 and TGF-beta1 in response to islet antigen. |
| 1758 | 12657834 | In contrast, T cells from anti-ICAM-1/LFA-1-treated mice expressed IFN-gamma, IL-10 and TGF-beta1 but not IL-4. |
| 1759 | 12711326 | Prevention of autoimmune diabetes in NOD mice by troglitazone is associated with modulation of ICAM-1 expression on pancreatic islet cells and IFN-gamma expression in splenic T cells. |
| 1760 | 12711326 | Thiazolidinediones acting as PPAR-gamma agonists are a new generation of oral antidiabetics addressing insulin resistance as a main feature of type-2 diabetes. |
| 1761 | 12711326 | To investigate whether TGZ acts by affecting the ICAM-1/LFA-1 pathway and/or the Th1/Th2 cytokine balance in NOD mice, we analysed the IL-1beta-induced ICAM-1 expression on islet-cells and the LFA-1, CD25, IL-2, IFN-gamma, IL-4, and IL-10 expression on splenocytes. |
| 1762 | 12711326 | After 200 days of oral TGZ administration, islet cells from TGZ-treated NOD mice showed a reduced ICAM-1 expression in response to the pro-inflammatory cytokine IL-1beta. |
| 1763 | 12711326 | The expression of the ligand LFA-1 on CD4(+) and CD8(+) T-cells was comparable to that of placebo- and untreated controls. |
| 1764 | 12748907 | Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos. |
| 1765 | 12748907 | In the search for genes involved in type 1 diabetes (T1D), other than the well-established risk alleles at the human leukocyte antigen loci, we have investigated the association and interaction of polymorphisms in genes involved in the IL4/IL13 pathway in a sample of 90 Filipino patients with T1D and 94 controls. |
| 1766 | 12748907 | We found that both individual SNPs (IL4R L389L; odds ratio [OR] 0.34; 95% confidence interval [CI] 0.17-0.67; P=.001) and specific haplotypes both in IL4R (OR 0.10; 95% CI 0-0.5; P=.001) and for the five linked IL4 and IL13 SNPs (OR 3.47; P=.004) were strongly associated with susceptibility to T1D. |
| 1767 | 12748907 | Since IL4 and IL13 both serve as ligands for a receptor composed, in part, of the IL4R alpha chain, we looked for potential epistasis between polymorphisms in the IL4R locus on chromosome 16p11 and the five SNPs in the IL4 and IL13 loci on chromosome 5q31 and found, through use of a logistic-regression model, significant gene-gene interactions (P=.045, corrected for multiple comparisons by permutation analysis). |
| 1768 | 12748907 | Our data suggest that the risk for T1D is determined, in part, by polymorphisms within the IL4R locus, including promoter and coding-sequence variants, and by specific combinations of genotypes at the IL4R and the IL4 and IL13 loci. |
| 1769 | 12748907 | Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos. |
| 1770 | 12748907 | In the search for genes involved in type 1 diabetes (T1D), other than the well-established risk alleles at the human leukocyte antigen loci, we have investigated the association and interaction of polymorphisms in genes involved in the IL4/IL13 pathway in a sample of 90 Filipino patients with T1D and 94 controls. |
| 1771 | 12748907 | We found that both individual SNPs (IL4R L389L; odds ratio [OR] 0.34; 95% confidence interval [CI] 0.17-0.67; P=.001) and specific haplotypes both in IL4R (OR 0.10; 95% CI 0-0.5; P=.001) and for the five linked IL4 and IL13 SNPs (OR 3.47; P=.004) were strongly associated with susceptibility to T1D. |
| 1772 | 12748907 | Since IL4 and IL13 both serve as ligands for a receptor composed, in part, of the IL4R alpha chain, we looked for potential epistasis between polymorphisms in the IL4R locus on chromosome 16p11 and the five SNPs in the IL4 and IL13 loci on chromosome 5q31 and found, through use of a logistic-regression model, significant gene-gene interactions (P=.045, corrected for multiple comparisons by permutation analysis). |
| 1773 | 12748907 | Our data suggest that the risk for T1D is determined, in part, by polymorphisms within the IL4R locus, including promoter and coding-sequence variants, and by specific combinations of genotypes at the IL4R and the IL4 and IL13 loci. |
| 1774 | 12748907 | Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos. |
| 1775 | 12748907 | In the search for genes involved in type 1 diabetes (T1D), other than the well-established risk alleles at the human leukocyte antigen loci, we have investigated the association and interaction of polymorphisms in genes involved in the IL4/IL13 pathway in a sample of 90 Filipino patients with T1D and 94 controls. |
| 1776 | 12748907 | We found that both individual SNPs (IL4R L389L; odds ratio [OR] 0.34; 95% confidence interval [CI] 0.17-0.67; P=.001) and specific haplotypes both in IL4R (OR 0.10; 95% CI 0-0.5; P=.001) and for the five linked IL4 and IL13 SNPs (OR 3.47; P=.004) were strongly associated with susceptibility to T1D. |
| 1777 | 12748907 | Since IL4 and IL13 both serve as ligands for a receptor composed, in part, of the IL4R alpha chain, we looked for potential epistasis between polymorphisms in the IL4R locus on chromosome 16p11 and the five SNPs in the IL4 and IL13 loci on chromosome 5q31 and found, through use of a logistic-regression model, significant gene-gene interactions (P=.045, corrected for multiple comparisons by permutation analysis). |
| 1778 | 12748907 | Our data suggest that the risk for T1D is determined, in part, by polymorphisms within the IL4R locus, including promoter and coding-sequence variants, and by specific combinations of genotypes at the IL4R and the IL4 and IL13 loci. |
| 1779 | 12748907 | Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos. |
| 1780 | 12748907 | In the search for genes involved in type 1 diabetes (T1D), other than the well-established risk alleles at the human leukocyte antigen loci, we have investigated the association and interaction of polymorphisms in genes involved in the IL4/IL13 pathway in a sample of 90 Filipino patients with T1D and 94 controls. |
| 1781 | 12748907 | We found that both individual SNPs (IL4R L389L; odds ratio [OR] 0.34; 95% confidence interval [CI] 0.17-0.67; P=.001) and specific haplotypes both in IL4R (OR 0.10; 95% CI 0-0.5; P=.001) and for the five linked IL4 and IL13 SNPs (OR 3.47; P=.004) were strongly associated with susceptibility to T1D. |
| 1782 | 12748907 | Since IL4 and IL13 both serve as ligands for a receptor composed, in part, of the IL4R alpha chain, we looked for potential epistasis between polymorphisms in the IL4R locus on chromosome 16p11 and the five SNPs in the IL4 and IL13 loci on chromosome 5q31 and found, through use of a logistic-regression model, significant gene-gene interactions (P=.045, corrected for multiple comparisons by permutation analysis). |
| 1783 | 12748907 | Our data suggest that the risk for T1D is determined, in part, by polymorphisms within the IL4R locus, including promoter and coding-sequence variants, and by specific combinations of genotypes at the IL4R and the IL4 and IL13 loci. |
| 1784 | 12748907 | Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos. |
| 1785 | 12748907 | In the search for genes involved in type 1 diabetes (T1D), other than the well-established risk alleles at the human leukocyte antigen loci, we have investigated the association and interaction of polymorphisms in genes involved in the IL4/IL13 pathway in a sample of 90 Filipino patients with T1D and 94 controls. |
| 1786 | 12748907 | We found that both individual SNPs (IL4R L389L; odds ratio [OR] 0.34; 95% confidence interval [CI] 0.17-0.67; P=.001) and specific haplotypes both in IL4R (OR 0.10; 95% CI 0-0.5; P=.001) and for the five linked IL4 and IL13 SNPs (OR 3.47; P=.004) were strongly associated with susceptibility to T1D. |
| 1787 | 12748907 | Since IL4 and IL13 both serve as ligands for a receptor composed, in part, of the IL4R alpha chain, we looked for potential epistasis between polymorphisms in the IL4R locus on chromosome 16p11 and the five SNPs in the IL4 and IL13 loci on chromosome 5q31 and found, through use of a logistic-regression model, significant gene-gene interactions (P=.045, corrected for multiple comparisons by permutation analysis). |
| 1788 | 12748907 | Our data suggest that the risk for T1D is determined, in part, by polymorphisms within the IL4R locus, including promoter and coding-sequence variants, and by specific combinations of genotypes at the IL4R and the IL4 and IL13 loci. |
| 1789 | 12763479 | TCR-activated NOD splenic CD4+ and CD8+ T cells are more resistant to AICD than control strain C57BL/6, BALB/c, and NOR T cells. |
| 1790 | 12763479 | NOR CD4+ but not CD8+ T cells are resistant to TCR-induced AICD. |
| 1791 | 12763479 | Whereas c-FLIP expression is reduced in activated T cells from control strains, it persists in activated NOD CD8+ T cells and is accompanied by diminished activity of caspase-3 and -8. |
| 1792 | 12763479 | IL-4 reduces this c-FLIP expression and increases caspase-3 and -8 activity in activated NOD CD8+ T cells. |
| 1793 | 12763479 | Moreover, IL-4 and CD28 costimulation restores the susceptibility of NOD CD8+ T cells to AICD, and this is associated with increased expression of CD25, CD95, CD95L, and TNFR2. |
| 1794 | 12763479 | TCR-activated NOD splenic CD4+ and CD8+ T cells are more resistant to AICD than control strain C57BL/6, BALB/c, and NOR T cells. |
| 1795 | 12763479 | NOR CD4+ but not CD8+ T cells are resistant to TCR-induced AICD. |
| 1796 | 12763479 | Whereas c-FLIP expression is reduced in activated T cells from control strains, it persists in activated NOD CD8+ T cells and is accompanied by diminished activity of caspase-3 and -8. |
| 1797 | 12763479 | IL-4 reduces this c-FLIP expression and increases caspase-3 and -8 activity in activated NOD CD8+ T cells. |
| 1798 | 12763479 | Moreover, IL-4 and CD28 costimulation restores the susceptibility of NOD CD8+ T cells to AICD, and this is associated with increased expression of CD25, CD95, CD95L, and TNFR2. |
| 1799 | 12765955 | Reduced insulitis in L-AGE versus H-AGE mice (P < 0.01) was marked by GAD- and insulin-unresponsive pancreatic interleukin (IL)-4-positive CD4+ cells compared with the GAD- and insulin-responsive interferon (IFN)-gamma-positive T-cells from H-AGE mice (P < 0.005). |
| 1800 | 12765955 | Splenocytes from L-AGE mice consisted of GAD- and insulin-responsive IL-10-positive CD4+ cells compared with the IFN-gamma-positive T-cells from H-AGE mice (P < 0.005). |
| 1801 | 12817032 | NOD recipient mice immunized with pDNA encoding a glutamic acid decarboxylase 65 (GAD65)-IgFc fusion protein (JwGAD65), IL-4 (JwIL4), and IL-10 (pIL10) exhibited an increased number of intact pro-islets expressing high levels of insulin 15 wk posttransplant, relative to NOD recipient mice immunized with pDNA encoding a hen egg lysozyme (HEL)-IgFc fusion protein (JwHEL)+JwIL4 and pIL10 or left untreated. |
| 1802 | 12817032 | Efficient protection of pro-islet grafts correlated with a marked reduction in GAD65-specific IFN-gamma reactivity and an increase in IL-10-secreting T cells. |
| 1803 | 12887099 | I-A.Y secreted IL-4, TGF-beta and IL-10 while I-A.D T cell line secreted IL-10 and IFN-gamma. |
| 1804 | 12941768 | In addition, the densities of IL-1 alpha- and IL-4-positive cells detected by immunohistochemistry and IL-4 mRNA-expressing cells evaluated by in situ hybridization were increased in the lamina propria in patients with type 1 diabetes and normal mucosa. |
| 1805 | 12941768 | Instead, the densities of IL-2, gamma-interferon (IFN-gamma), and tumor necrosis factor alpha-positive cells, the density of IFN-gamma mRNA positive cells, and the amounts of IFN-gamma mRNA detected by RT-PCR correlated with the degree of celiac disease in patients with type 1 diabetes. |
| 1806 | 14500690 | Islet allograft rejection in nonobese diabetic mice involves the common gamma-chain and CD28/CD154-dependent and -independent mechanisms. |
| 1807 | 14500690 | In the present study we tested the hypothesis that islet allograft survival in the diabetic NOD mouse is determined by the interplay of diverse islet-specific T cell subsets whose activation is regulated by CD28/CD154 costimulatory signals and the common gamma-chain (gammac; a shared signaling element by receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21). |
| 1808 | 14500690 | We found that common gammac blockade is remarkably effective in blocking the onset and the ongoing autoimmune diabetes, whereas CD28/CD154 blockade has no effect in suppressing the ongoing diabetes. |
| 1809 | 14500690 | However, CD28/CD154 blockade completely blocks the alloimmune-mediated islet rejection. |
| 1810 | 14500690 | Also, a subset of memory-like T cells in the NOD mice is resistant to CD28/CD154 blockade, but is sensitive to the common gammac blockade. |
| 1811 | 14500690 | Nonetheless, neither common gammac blockade nor CD28/CD154 blockade can prevent islet allograft rejection in diabetic NOD mice. |
| 1812 | 14500690 | Treatment of diabetic NOD recipients with CD28/CD154 blockade plus gammac blockade markedly prolongs islet allograft survival compared with the controls. |
| 1813 | 14500690 | We concluded that the effector mechanisms in diabetic NOD hosts are inherently complex, and rejection in this model involves CD28/CD154/gammac-dependent and -independent mechanisms. |
| 1814 | 14508150 | The insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha, interleukin-6, macrophage migration inhibitory factor and other pro-inflammatory cytokines, and free radicals; and enhances the synthesis of endothelial nitric oxide and anti-inflammatory cytokines interleukin-4 and interleukin-10. |
| 1815 | 14530324 | CD4(+)CD25(-) T cells showed a higher proliferation and produced more IFN-gamma, but less IL-4 and IL-10, whereas CD4(+)CD25(+) T suppressor cells produced significantly lower levels of IL-10 in 16- compared with 8-wk-old NOD mice. |
| 1816 | 14530324 | An increased percentage of CD4(+)CD25(-) T cells expressing CD54 was present in 16-wk-old and in diabetic NOD, but not in BALB/c mice. |
| 1817 | 14530324 | Costimulation via CD54 increased the proliferation of CD4(+)CD25(-) T cells from 16-, but not 8-wk-old NOD mice, and blocking CD54 prevented their proliferation, consistent with the role of CD54 in diabetes development. |
| 1818 | 14561205 | These regulatory T cells produce down-regulatory cytokines such as IL4, IL10 and TGFbeta, a Th2 / Th3 cytokine pattern. |
| 1819 | 14563017 | Functional studies using monoclonal antibodies indicate that the CD72c allele of NOD can serve as a positive regulator of B cell responses both as a single signal and in synergy with BCR or IL-4 stimulation. |
| 1820 | 14568923 | Thymic-derived dysregulated tolerance has been suggested to occur in type 1 diabetes via impaired generation of CD4(+)CD25(+) T regulatory cells, leading to autoimmune beta cell destruction. |
| 1821 | 14568923 | In this study, we demonstrate that Notch3 expression is a characteristic feature of CD4(+)CD25(+) cells. |
| 1822 | 14568923 | The failure to develop the disease is associated with an increase of CD4(+)CD25(+) T regulatory cells, accumulating in lymphoid organs, in pancreas infiltrates and paralleled by increased expression of IL-4 and IL-10. |
| 1823 | 14568923 | Accordingly, CD4(+) T cells from Notch3-transgenic mice inhibit the development of hyperglycemia and insulitis when injected into streptozotocin-treated wild-type mice and display in vitro suppressive activity. |
| 1824 | 14592922 | These cells, transduced with retroviral vectors to drive expression of various "regulatory proteins" such as IL-4, IL-10, IL-12p40, and anti-TNF scFv, deliver these immunoregulatory proteins to the inflamed lesions, providing therapy for experimental autoimmune encephalitis (EAE), collagen-induced arthritis (CIA), and nonobese diabetic mice (NOD). |
| 1825 | 14609217 | First, gene microarray analyses showed that alpha-GalCer treatment decreases interleukin (IL)16 and increases IL10 and MIP1beta gene expression in the spleen. |
| 1826 | 14609217 | Anti-IL16 antibody treatment protects NOD mice against insulitis and T1D, and neutralization of MIP1beta abrogates IL4 induced protection from T1D. |
| 1827 | 14609217 | By controlling the expression and activity of IL16 and MIP1beta alpha-GalCer treatment may modulate the number, localization and function of NKT cells and regulate susceptibility to T1D. |
| 1828 | 14609223 | CD4+ lymphocytes with specificity for insulin can be induced by immunization with the insulin B chain via the oral route or by DNA vaccination. |
| 1829 | 14609223 | In comparison to non-regulatory insulin B-specific cell lines, they produce high amounts of interleukin (IL)4 and IL10, whereas interferon (IFN)gamma and tumour necrosis factor (TNF)alpha levels are comparable. |
| 1830 | 14609223 | We propose that this is achieved by modulation of antigen presenting cells that lose the ability to propagate aggressive responses after exposure to IL4 or IL10 in vitro. |
| 1831 | 14609223 | In order to avoid induction of insulin B-specific autoaggressive T cells we have demonstrated that administration of IL4 or IL10 at the time of immunization is beneficial and therefore should be part of a potential future clinical application. |
| 1832 | 14609223 | CD4+ lymphocytes with specificity for insulin can be induced by immunization with the insulin B chain via the oral route or by DNA vaccination. |
| 1833 | 14609223 | In comparison to non-regulatory insulin B-specific cell lines, they produce high amounts of interleukin (IL)4 and IL10, whereas interferon (IFN)gamma and tumour necrosis factor (TNF)alpha levels are comparable. |
| 1834 | 14609223 | We propose that this is achieved by modulation of antigen presenting cells that lose the ability to propagate aggressive responses after exposure to IL4 or IL10 in vitro. |
| 1835 | 14609223 | In order to avoid induction of insulin B-specific autoaggressive T cells we have demonstrated that administration of IL4 or IL10 at the time of immunization is beneficial and therefore should be part of a potential future clinical application. |
| 1836 | 14609223 | CD4+ lymphocytes with specificity for insulin can be induced by immunization with the insulin B chain via the oral route or by DNA vaccination. |
| 1837 | 14609223 | In comparison to non-regulatory insulin B-specific cell lines, they produce high amounts of interleukin (IL)4 and IL10, whereas interferon (IFN)gamma and tumour necrosis factor (TNF)alpha levels are comparable. |
| 1838 | 14609223 | We propose that this is achieved by modulation of antigen presenting cells that lose the ability to propagate aggressive responses after exposure to IL4 or IL10 in vitro. |
| 1839 | 14609223 | In order to avoid induction of insulin B-specific autoaggressive T cells we have demonstrated that administration of IL4 or IL10 at the time of immunization is beneficial and therefore should be part of a potential future clinical application. |
| 1840 | 14632742 | Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice. |
| 1841 | 14632742 | CD11c+/CD11b+dendritic cells (DC) with high levels of major histocompatibility complex (MHC) class II and co-stimulatory molecules have been derived from spleen cells cultured with granulocyte-macrophage colony stimulating factor (GM-CSF) + flt-3L + interleukin (IL)-6 (flt-3L-DC). |
| 1842 | 14632742 | In contrast, DC derived from bone marrow cells cultured with GM-CSF + IL-4 [bone marrow (BM)-DC] induced no protection. |
| 1843 | 14632742 | Moreover, protection against diabetes following injection of flt-3L-DC was associated with IL-4 and IL-10 production in the spleen and the pancreatic lymph nodes of recipient mice, indicating that this DC population is able to polarize the immune response towards a Th2 pathway. |
| 1844 | 14632742 | Our findings show that a subset of DC, characterized by a mature phenotype and the absence of IL-12p70 production can be derived from NOD mouse spleen favouring IL-4 and IL-10 regulatory responses and protection from diabetes development. |
| 1845 | 14632742 | Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice. |
| 1846 | 14632742 | CD11c+/CD11b+dendritic cells (DC) with high levels of major histocompatibility complex (MHC) class II and co-stimulatory molecules have been derived from spleen cells cultured with granulocyte-macrophage colony stimulating factor (GM-CSF) + flt-3L + interleukin (IL)-6 (flt-3L-DC). |
| 1847 | 14632742 | In contrast, DC derived from bone marrow cells cultured with GM-CSF + IL-4 [bone marrow (BM)-DC] induced no protection. |
| 1848 | 14632742 | Moreover, protection against diabetes following injection of flt-3L-DC was associated with IL-4 and IL-10 production in the spleen and the pancreatic lymph nodes of recipient mice, indicating that this DC population is able to polarize the immune response towards a Th2 pathway. |
| 1849 | 14632742 | Our findings show that a subset of DC, characterized by a mature phenotype and the absence of IL-12p70 production can be derived from NOD mouse spleen favouring IL-4 and IL-10 regulatory responses and protection from diabetes development. |
| 1850 | 14632742 | Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice. |
| 1851 | 14632742 | CD11c+/CD11b+dendritic cells (DC) with high levels of major histocompatibility complex (MHC) class II and co-stimulatory molecules have been derived from spleen cells cultured with granulocyte-macrophage colony stimulating factor (GM-CSF) + flt-3L + interleukin (IL)-6 (flt-3L-DC). |
| 1852 | 14632742 | In contrast, DC derived from bone marrow cells cultured with GM-CSF + IL-4 [bone marrow (BM)-DC] induced no protection. |
| 1853 | 14632742 | Moreover, protection against diabetes following injection of flt-3L-DC was associated with IL-4 and IL-10 production in the spleen and the pancreatic lymph nodes of recipient mice, indicating that this DC population is able to polarize the immune response towards a Th2 pathway. |
| 1854 | 14632742 | Our findings show that a subset of DC, characterized by a mature phenotype and the absence of IL-12p70 production can be derived from NOD mouse spleen favouring IL-4 and IL-10 regulatory responses and protection from diabetes development. |
| 1855 | 14632742 | Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice. |
| 1856 | 14632742 | CD11c+/CD11b+dendritic cells (DC) with high levels of major histocompatibility complex (MHC) class II and co-stimulatory molecules have been derived from spleen cells cultured with granulocyte-macrophage colony stimulating factor (GM-CSF) + flt-3L + interleukin (IL)-6 (flt-3L-DC). |
| 1857 | 14632742 | In contrast, DC derived from bone marrow cells cultured with GM-CSF + IL-4 [bone marrow (BM)-DC] induced no protection. |
| 1858 | 14632742 | Moreover, protection against diabetes following injection of flt-3L-DC was associated with IL-4 and IL-10 production in the spleen and the pancreatic lymph nodes of recipient mice, indicating that this DC population is able to polarize the immune response towards a Th2 pathway. |
| 1859 | 14632742 | Our findings show that a subset of DC, characterized by a mature phenotype and the absence of IL-12p70 production can be derived from NOD mouse spleen favouring IL-4 and IL-10 regulatory responses and protection from diabetes development. |
| 1860 | 14634066 | Expression of CD11c, CD40, CD54, and major histocompatibility complex I-A(g7) was reduced in cells cultured with additional DcR3.Fc, compared with DCs incubated with granulocyte macrophage-colony stimulating factor and interleukin (IL)-4, indicating that DcR3 interferes with the differentiation and maturation of BM-DCs. |
| 1861 | 14634066 | One of the most striking effects of DcR3.Fc on the differentiation of DCs was the up-regulation of CD86 and down-regulation of CD80, suggesting a modulatory potential to skew the T cell response toward the T helper cell type 2 (Th2) phenotype. |
| 1862 | 14634066 | Moreover, the secretion of interferon-gamma from T cells cocultured with DcR3.Fc-treated DCs was profoundly suppressed, indicating that DcR3 exerts a Th1-suppressing effect on differentiating DCs. |
| 1863 | 14634066 | Data from two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight analysis show an up-regulation of some proteins-such as mitogen-activated protein kinase p38 beta, cyclin-dependent kinase 6, and signal-induced proliferation-associated gene 1-and a down-regulation of the IL-17 precursor; tumor necrosis factor-related apoptosis-inducing ligand family member-associated nuclear factor-kappaB activator-binding kinase 1; and Golgi S-nitroso-N-acetylpenicillamine in cells treated with DcR3, further demonstrating its effect on DC differentiation and function. |
| 1864 | 14679078 | We correlated T and B cell responses to insulin in subjects with increased genetic risk (HLA-DRB1*04, DQB1*0302) for diabetes with or without islet autoantibodies (Ab+ subjects and controls, respectively) and HLA-matched patients. |
| 1865 | 14679078 | Peripheral blood mononuclear cells were stimulated with 15 overlapping proinsulin peptides (16-mer), and proinflammatory Th1 (IFNgamma) and anti-inflammatory Th2 (IL-4) cytokines were analyzed. |
| 1866 | 14679078 | We observed a simultaneous increase in IL-4 and IFNgamma secretion in early islet autoimmunity of Ab+ subjects, but not in insulin-treated T1D patients. |
| 1867 | 14679078 | Furthermore, the increase in IL-4 secretion in Ab+ subjects was associated with insulin autoantibody responses. |
| 1868 | 14679078 | There was no correlation of either IFNgamma or IL-4 secretion with insulin antibody responses in patients already treated with exogenous insulin. |
| 1869 | 14679078 | We correlated T and B cell responses to insulin in subjects with increased genetic risk (HLA-DRB1*04, DQB1*0302) for diabetes with or without islet autoantibodies (Ab+ subjects and controls, respectively) and HLA-matched patients. |
| 1870 | 14679078 | Peripheral blood mononuclear cells were stimulated with 15 overlapping proinsulin peptides (16-mer), and proinflammatory Th1 (IFNgamma) and anti-inflammatory Th2 (IL-4) cytokines were analyzed. |
| 1871 | 14679078 | We observed a simultaneous increase in IL-4 and IFNgamma secretion in early islet autoimmunity of Ab+ subjects, but not in insulin-treated T1D patients. |
| 1872 | 14679078 | Furthermore, the increase in IL-4 secretion in Ab+ subjects was associated with insulin autoantibody responses. |
| 1873 | 14679078 | There was no correlation of either IFNgamma or IL-4 secretion with insulin antibody responses in patients already treated with exogenous insulin. |
| 1874 | 14679078 | We correlated T and B cell responses to insulin in subjects with increased genetic risk (HLA-DRB1*04, DQB1*0302) for diabetes with or without islet autoantibodies (Ab+ subjects and controls, respectively) and HLA-matched patients. |
| 1875 | 14679078 | Peripheral blood mononuclear cells were stimulated with 15 overlapping proinsulin peptides (16-mer), and proinflammatory Th1 (IFNgamma) and anti-inflammatory Th2 (IL-4) cytokines were analyzed. |
| 1876 | 14679078 | We observed a simultaneous increase in IL-4 and IFNgamma secretion in early islet autoimmunity of Ab+ subjects, but not in insulin-treated T1D patients. |
| 1877 | 14679078 | Furthermore, the increase in IL-4 secretion in Ab+ subjects was associated with insulin autoantibody responses. |
| 1878 | 14679078 | There was no correlation of either IFNgamma or IL-4 secretion with insulin antibody responses in patients already treated with exogenous insulin. |
| 1879 | 14679078 | We correlated T and B cell responses to insulin in subjects with increased genetic risk (HLA-DRB1*04, DQB1*0302) for diabetes with or without islet autoantibodies (Ab+ subjects and controls, respectively) and HLA-matched patients. |
| 1880 | 14679078 | Peripheral blood mononuclear cells were stimulated with 15 overlapping proinsulin peptides (16-mer), and proinflammatory Th1 (IFNgamma) and anti-inflammatory Th2 (IL-4) cytokines were analyzed. |
| 1881 | 14679078 | We observed a simultaneous increase in IL-4 and IFNgamma secretion in early islet autoimmunity of Ab+ subjects, but not in insulin-treated T1D patients. |
| 1882 | 14679078 | Furthermore, the increase in IL-4 secretion in Ab+ subjects was associated with insulin autoantibody responses. |
| 1883 | 14679078 | There was no correlation of either IFNgamma or IL-4 secretion with insulin antibody responses in patients already treated with exogenous insulin. |
| 1884 | 14688338 | Third, the application of cholera toxin to the intact skin of NOD/Lt mice, with or without insulin B peptide 9-23, exacerbated insulitis and T lymphocyte-derived IFN-gamma and IL-4 production in the islets of Langerhans, resulting in an increased incidence and rate of onset of autoimmune diabetes. |
| 1885 | 14712310 | IL4R encodes a subunit of the interleukin-4 receptor, a molecule important for T-cell development and differentiation, and is a gene shown to be associated with immune-related diseases such as asthma and type I diabetes. |
| 1886 | 14735147 | Genetic association with type 1 diabetes (T1D) has been established for two chromosomal regions: HLA DQ/DR (IDDM1) and INS VNTR (IDDM2). |
| 1887 | 14735147 | Functional genetic polymorphisms of proinflammatory (T-helper-1: IL-2, IL-12 and IFN-gamma), anti-inflammatory (T-helper-2: IL-4, IL-6 and IL-10) and metabolic (IGF-I, VDR and INS) genes were determined in 206 Dutch simplex families with juvenile onset T1D and the results were analysed using the transmission disequilibrium test. |
| 1888 | 14735147 | Significantly increased transmission to T1D probands was observed for the loci IDDM1, IDDM2 and the vitamin D receptor. |
| 1889 | 14735147 | Although none of the other individual polymorphisms was associated with disease individually, the combination of T-helper-2 and metabolic/growth alleles IL-10(*)R2, IL-4(*)C, VDR(*)C and IGF-I(*)wt was found to be transmitted more frequently than expected (67%, P(c)=0.015). |
| 1890 | 14735147 | Genetic association with type 1 diabetes (T1D) has been established for two chromosomal regions: HLA DQ/DR (IDDM1) and INS VNTR (IDDM2). |
| 1891 | 14735147 | Functional genetic polymorphisms of proinflammatory (T-helper-1: IL-2, IL-12 and IFN-gamma), anti-inflammatory (T-helper-2: IL-4, IL-6 and IL-10) and metabolic (IGF-I, VDR and INS) genes were determined in 206 Dutch simplex families with juvenile onset T1D and the results were analysed using the transmission disequilibrium test. |
| 1892 | 14735147 | Significantly increased transmission to T1D probands was observed for the loci IDDM1, IDDM2 and the vitamin D receptor. |
| 1893 | 14735147 | Although none of the other individual polymorphisms was associated with disease individually, the combination of T-helper-2 and metabolic/growth alleles IL-10(*)R2, IL-4(*)C, VDR(*)C and IGF-I(*)wt was found to be transmitted more frequently than expected (67%, P(c)=0.015). |
| 1894 | 14741738 | The p38 mitogen-activated protein kinase (MAPK) pathway is important in Th1 immunity, macrophage activation, and apoptosis. |
| 1895 | 14741738 | Since they may be associated with beta-cell destruction during the development of type 1 diabetes, we investigated the role of the p38 MAPK pathway in female nonobese diabetic (NOD) mice. |
| 1896 | 14741738 | Phosphorylated p38 MAPK was observed immunohistochemically in CD4+ cells that had infiltrated into the islets and part of beta-cells, increasing in proportion to the severity of insulitis. |
| 1897 | 14741738 | Continuous oral administration of 0.08% FR167653, a specific p38 MAPK pathway inhibitor, significantly reduced the ex vivo production of interferon-gamma by splenic Th1 cells without affecting interleukin-4 production by Th2 cells. |
| 1898 | 14741738 | Treatment with FR167653 after insulitis had developed (i.e. from 10-30 weeks of age) also prevented diabetes, further suggesting that treatment with the p38 MAPK pathway inhibitor keeps insulitis benign in NOD mice, partly by inhibiting Th1 immunity. |
| 1899 | 14741738 | These findings suggest that p38 MAPK is a key mediator that switches insulitis from benign to destructive in the development of type 1 diabetes. |
| 1900 | 14768037 | These hallmarks of allergic asthma were associated with increased IL-4, IL-5, IL-13 and eotaxin production in the lungs, as compared with BALB/c mice. |
| 1901 | 14768049 | However, in vivo neutralization of IL-4, IL-10 or TGF-beta using monoclonal antibodies did not prevent the inhibition whereas treatment with an antibody against the glucocorticoid-induced TNF receptor abrogated the protection from disease. |
| 1902 | 14965001 | Content of different cytokines (IF alpha, TNF alpha, IL-1 alpha, IL-4, IL-6 and IL-10) was examined in the blood serum in two groups of healthy children-siblings with type 1 diabetes mellitus with and without revealed insulin autoantibodies against pancreatic islets (GADA, IA-2A and IAA) by enzyme-like immunosorbent assay (ELISA). |
| 1903 | 14965001 | In the group of patients with two and more revealed autoantibodies the higher indices in the number of IF alpha, TNF alpha and IL-6, and the decrease in the level of IL-4 comparing with the group of children with negative reaction to diabetes associated autoantibodies were more often observed. |
| 1904 | 14965001 | Content of different cytokines (IF alpha, TNF alpha, IL-1 alpha, IL-4, IL-6 and IL-10) was examined in the blood serum in two groups of healthy children-siblings with type 1 diabetes mellitus with and without revealed insulin autoantibodies against pancreatic islets (GADA, IA-2A and IAA) by enzyme-like immunosorbent assay (ELISA). |
| 1905 | 14965001 | In the group of patients with two and more revealed autoantibodies the higher indices in the number of IF alpha, TNF alpha and IL-6, and the decrease in the level of IL-4 comparing with the group of children with negative reaction to diabetes associated autoantibodies were more often observed. |
| 1906 | 15024185 | The expression of cytokine genes in the peritoneal macrophages and splenic CD4- and CD8-positive lymphocytes of the nonobese diabetic mice. |
| 1907 | 15024185 | In this study, we showed that the mRNA expression of the pro-inflammatory cytokines, TNF-alpha, IL-1 beta, IL-6, and GM-CSF, were increased while the anti-inflammatory cytokine, TGF-beta, decreased in the peritoneal macrophages of nonobese diabetic (NOD) mice. |
| 1908 | 15024185 | Surprisingly the expression of IFN-gamma and IL-2 by splenic CD4+ cells were lower in 5-week-old NOD mice as compared to the nonobese diabetic resistant (NOR) control mice, but their expression was higher in older NOD mice. |
| 1909 | 15024185 | The expression of IL-4 and IL-10 decreased in splenic CD4-positive lymphocytes. |
| 1910 | 15024185 | Splenic CD8-positive lymphocytes expressed increased levels of IFN-gamma and IL-10 but the latter decreased sharply when diabetes occurred. |
| 1911 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 1912 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 1913 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 1914 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 1915 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 1916 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 1917 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 1918 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 1919 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 1920 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 1921 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 1922 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 1923 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 1924 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 1925 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 1926 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 1927 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 1928 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 1929 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 1930 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 1931 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 1932 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 1933 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 1934 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 1935 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 1936 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 1937 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 1938 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 1939 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 1940 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 1941 | 15056761 | Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. |
| 1942 | 15056761 | In this study, human GAD65 (hGAD65), as well as murine IL-4, was expressed in transgenic plants for feeding trials. |
| 1943 | 15056761 | Both IL-4 and hGAD65 plant tissue were required to protect nonobese diabetic mice from diabetes, and no benefit was found if either was used alone. |
| 1944 | 15056761 | Combined therapy enhanced levels of IgG1 anti-GAD antibodies, increased splenocyte IL-4/IFN-gamma cytokine responses, and produced protective regulatory T cells. |
| 1945 | 15056761 | These results demonstrate that orally administered plant IL-4 remains biologically active and is synergistic when given with hGAD65 in inducing robust oral immune tolerance. |
| 1946 | 15056761 | Using transgenic plants expressing IL-4 and GAD65 may be a novel clinical approach to the prevention of human type 1 diabetes by oral tolerance. |
| 1947 | 15093559 | Insulin autoantibodies (P < 0.01) and insulitis scores (P < 0.02) were reduced, and intra-pancreatic IL-4 mRNA increased (P < 0.05) in wheat and barley protein-deprived mice. |
| 1948 | 15096655 | Interleukin-11 inhibits NF-kappaB and AP-1 activation in islets and prevents diabetes induced with streptozotocin in mice. |
| 1949 | 15096655 | This laboratory has reported that multiple low doses of streptozotocin (MLD-STZ) similarly upregulate the T helper (Th)1-type proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in islets of both the diabetes-susceptible male and the diabetes-resistant female C57BL/6 mice and that MLD-STZ downregulates the anti-inflammatory Th2-type cytokines interleukin (IL)-4 and IL-10, as well as the anti-inflammatory Th3-type cytokine-transforming growth factor (TGF)-ss1 in islets of male, but not female, mice. |
| 1950 | 15096655 | Here, we investigated the effects of MLD-STZ on the anti-inflammatory cytokine IL-11 and the transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1, which are involved in gene activation of proinflammatory cytokines, and on the cytosolic kinase (IKK-alpha) of NF-kappaB inhibitor (IkappaB). |
| 1951 | 15096655 | Furthermore, the effect of recombinant human (rh)IL-11 on MLD-STZ diabetes, insulitis, cytokines, IKK-alpha, NF-kappaB, and AP-1 was analyzed in islets. |
| 1952 | 15096655 | Interleukin-11 prevented diabetes without affecting insulitis; attenuated TNF-alpha and IFN-gamma response; and stimulated IL-4 production and inhibited activation of IKK-alpha, NF-kappaB, and AP-1. |
| 1953 | 15096655 | In this process, the transcription factors NF-kappaB and AP-1 might play a key role. |
| 1954 | 15096655 | Interleukin-11 inhibits NF-kappaB and AP-1 activation in islets and prevents diabetes induced with streptozotocin in mice. |
| 1955 | 15096655 | This laboratory has reported that multiple low doses of streptozotocin (MLD-STZ) similarly upregulate the T helper (Th)1-type proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in islets of both the diabetes-susceptible male and the diabetes-resistant female C57BL/6 mice and that MLD-STZ downregulates the anti-inflammatory Th2-type cytokines interleukin (IL)-4 and IL-10, as well as the anti-inflammatory Th3-type cytokine-transforming growth factor (TGF)-ss1 in islets of male, but not female, mice. |
| 1956 | 15096655 | Here, we investigated the effects of MLD-STZ on the anti-inflammatory cytokine IL-11 and the transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1, which are involved in gene activation of proinflammatory cytokines, and on the cytosolic kinase (IKK-alpha) of NF-kappaB inhibitor (IkappaB). |
| 1957 | 15096655 | Furthermore, the effect of recombinant human (rh)IL-11 on MLD-STZ diabetes, insulitis, cytokines, IKK-alpha, NF-kappaB, and AP-1 was analyzed in islets. |
| 1958 | 15096655 | Interleukin-11 prevented diabetes without affecting insulitis; attenuated TNF-alpha and IFN-gamma response; and stimulated IL-4 production and inhibited activation of IKK-alpha, NF-kappaB, and AP-1. |
| 1959 | 15096655 | In this process, the transcription factors NF-kappaB and AP-1 might play a key role. |
| 1960 | 15100275 | A newly described population of NK cells that spontaneously secrete IL-4 and IFN-gamma is present in the intraepithelial lymphocyte compartment of the rat. |
| 1961 | 15100275 | Prediabetic BBDP and diabetes-resistant BB animals also exhibited defective IENK cell function, including decreased NK cell cytotoxicity and reduced secretion of IL-4 and IFN-gamma. |
| 1962 | 15100275 | A newly described population of NK cells that spontaneously secrete IL-4 and IFN-gamma is present in the intraepithelial lymphocyte compartment of the rat. |
| 1963 | 15100275 | Prediabetic BBDP and diabetes-resistant BB animals also exhibited defective IENK cell function, including decreased NK cell cytotoxicity and reduced secretion of IL-4 and IFN-gamma. |
| 1964 | 15111500 | Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells. |
| 1965 | 15111500 | Although interleukin (IL)-4 and IL-10 have been implicated in alpha-GalCer-induced protection from type 1 diabetes, a precise role for these cytokines in iNKT cell regulation of susceptibility to type 1 diabetes has not been identified. |
| 1966 | 15111500 | Here we use NOD.IL-4(-/-) and NOD.IL-10(-/-) knockout mice to further evaluate the roles of IL-4 and IL-10 in alpha-GalCer-induced protection from type 1 diabetes. |
| 1967 | 15111500 | We found that IL-4 but not IL-10 expression mediates protection against spontaneous type 1 diabetes, recurrent type 1 diabetes, and prolonged syngeneic islet graft function. |
| 1968 | 15111500 | Increased transforming growth factor-beta gene expression in pancreatic lymph nodes may be involved in alpha-GalCer-mediated protection in NOD.IL-10(-/-) knockout mice. |
| 1969 | 15111500 | Unlike the requirement of IL-7 and IL-15 to maintain iNKT cell homeostasis, IL-4 and IL-10 are not required for alpha-GalCer-induced iNKT cell expansion and/or survival. |
| 1970 | 15111500 | Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells. |
| 1971 | 15111500 | Although interleukin (IL)-4 and IL-10 have been implicated in alpha-GalCer-induced protection from type 1 diabetes, a precise role for these cytokines in iNKT cell regulation of susceptibility to type 1 diabetes has not been identified. |
| 1972 | 15111500 | Here we use NOD.IL-4(-/-) and NOD.IL-10(-/-) knockout mice to further evaluate the roles of IL-4 and IL-10 in alpha-GalCer-induced protection from type 1 diabetes. |
| 1973 | 15111500 | We found that IL-4 but not IL-10 expression mediates protection against spontaneous type 1 diabetes, recurrent type 1 diabetes, and prolonged syngeneic islet graft function. |
| 1974 | 15111500 | Increased transforming growth factor-beta gene expression in pancreatic lymph nodes may be involved in alpha-GalCer-mediated protection in NOD.IL-10(-/-) knockout mice. |
| 1975 | 15111500 | Unlike the requirement of IL-7 and IL-15 to maintain iNKT cell homeostasis, IL-4 and IL-10 are not required for alpha-GalCer-induced iNKT cell expansion and/or survival. |
| 1976 | 15111500 | Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells. |
| 1977 | 15111500 | Although interleukin (IL)-4 and IL-10 have been implicated in alpha-GalCer-induced protection from type 1 diabetes, a precise role for these cytokines in iNKT cell regulation of susceptibility to type 1 diabetes has not been identified. |
| 1978 | 15111500 | Here we use NOD.IL-4(-/-) and NOD.IL-10(-/-) knockout mice to further evaluate the roles of IL-4 and IL-10 in alpha-GalCer-induced protection from type 1 diabetes. |
| 1979 | 15111500 | We found that IL-4 but not IL-10 expression mediates protection against spontaneous type 1 diabetes, recurrent type 1 diabetes, and prolonged syngeneic islet graft function. |
| 1980 | 15111500 | Increased transforming growth factor-beta gene expression in pancreatic lymph nodes may be involved in alpha-GalCer-mediated protection in NOD.IL-10(-/-) knockout mice. |
| 1981 | 15111500 | Unlike the requirement of IL-7 and IL-15 to maintain iNKT cell homeostasis, IL-4 and IL-10 are not required for alpha-GalCer-induced iNKT cell expansion and/or survival. |
| 1982 | 15111500 | Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells. |
| 1983 | 15111500 | Although interleukin (IL)-4 and IL-10 have been implicated in alpha-GalCer-induced protection from type 1 diabetes, a precise role for these cytokines in iNKT cell regulation of susceptibility to type 1 diabetes has not been identified. |
| 1984 | 15111500 | Here we use NOD.IL-4(-/-) and NOD.IL-10(-/-) knockout mice to further evaluate the roles of IL-4 and IL-10 in alpha-GalCer-induced protection from type 1 diabetes. |
| 1985 | 15111500 | We found that IL-4 but not IL-10 expression mediates protection against spontaneous type 1 diabetes, recurrent type 1 diabetes, and prolonged syngeneic islet graft function. |
| 1986 | 15111500 | Increased transforming growth factor-beta gene expression in pancreatic lymph nodes may be involved in alpha-GalCer-mediated protection in NOD.IL-10(-/-) knockout mice. |
| 1987 | 15111500 | Unlike the requirement of IL-7 and IL-15 to maintain iNKT cell homeostasis, IL-4 and IL-10 are not required for alpha-GalCer-induced iNKT cell expansion and/or survival. |
| 1988 | 15111500 | Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells. |
| 1989 | 15111500 | Although interleukin (IL)-4 and IL-10 have been implicated in alpha-GalCer-induced protection from type 1 diabetes, a precise role for these cytokines in iNKT cell regulation of susceptibility to type 1 diabetes has not been identified. |
| 1990 | 15111500 | Here we use NOD.IL-4(-/-) and NOD.IL-10(-/-) knockout mice to further evaluate the roles of IL-4 and IL-10 in alpha-GalCer-induced protection from type 1 diabetes. |
| 1991 | 15111500 | We found that IL-4 but not IL-10 expression mediates protection against spontaneous type 1 diabetes, recurrent type 1 diabetes, and prolonged syngeneic islet graft function. |
| 1992 | 15111500 | Increased transforming growth factor-beta gene expression in pancreatic lymph nodes may be involved in alpha-GalCer-mediated protection in NOD.IL-10(-/-) knockout mice. |
| 1993 | 15111500 | Unlike the requirement of IL-7 and IL-15 to maintain iNKT cell homeostasis, IL-4 and IL-10 are not required for alpha-GalCer-induced iNKT cell expansion and/or survival. |
| 1994 | 15115315 | Type 1, or cellular, immune response is characterized by overproduction of IL-1, IL-2, IFN-gamma and TNF-alpha and is the underlying immune mechanism of some autoimmune disorders such as psoriasis, alopecia areata, rheumatoid arthritis, Crohn's disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis. |
| 1995 | 15115315 | Type 2 immune response is seen in allergic and antibody-mediated autoimmune diseases and is characterized by IL-4, IL-6 and IL-10 overproduction. |
| 1996 | 15115315 | PGE2 decreases the production of IL-1, IL-2, IFN-gamma and TNF-alpha and proliferation of TH1 cells and increases the production of IL-4, leading to suppression of the type 1 immune response. |
| 1997 | 15115315 | Type 1, or cellular, immune response is characterized by overproduction of IL-1, IL-2, IFN-gamma and TNF-alpha and is the underlying immune mechanism of some autoimmune disorders such as psoriasis, alopecia areata, rheumatoid arthritis, Crohn's disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis. |
| 1998 | 15115315 | Type 2 immune response is seen in allergic and antibody-mediated autoimmune diseases and is characterized by IL-4, IL-6 and IL-10 overproduction. |
| 1999 | 15115315 | PGE2 decreases the production of IL-1, IL-2, IFN-gamma and TNF-alpha and proliferation of TH1 cells and increases the production of IL-4, leading to suppression of the type 1 immune response. |
| 2000 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2001 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2002 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2003 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2004 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2005 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2006 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2007 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2008 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2009 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2010 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2011 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2012 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2013 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2014 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2015 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2016 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2017 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2018 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2019 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2020 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2021 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2022 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2023 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2024 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2025 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2026 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2027 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2028 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2029 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2030 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2031 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2032 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2033 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2034 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2035 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2036 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2037 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2038 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2039 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2040 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2041 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2042 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2043 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2044 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2045 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2046 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2047 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2048 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2049 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2050 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2051 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2052 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2053 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2054 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2055 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2056 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2057 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2058 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2059 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2060 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2061 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2062 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2063 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2064 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2065 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2066 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2067 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2068 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2069 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2070 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2071 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2072 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2073 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2074 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2075 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2076 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2077 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2078 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2079 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2080 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2081 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2082 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2083 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2084 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2085 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2086 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2087 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2088 | 15140063 | Expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-gamma, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD(65))-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin. |
| 2089 | 15140063 | During the first month, after diagnosis, the GAD(65)-peptide caused an increased ratio of IFN-gamma/IL-4 mRNA expression (P < 0.05) and increased secretion of IFN-gamma (P = 0.07). |
| 2090 | 15140063 | Expression of IFN-gamma mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. |
| 2091 | 15140063 | Expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-gamma, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD(65))-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin. |
| 2092 | 15140063 | During the first month, after diagnosis, the GAD(65)-peptide caused an increased ratio of IFN-gamma/IL-4 mRNA expression (P < 0.05) and increased secretion of IFN-gamma (P = 0.07). |
| 2093 | 15140063 | Expression of IFN-gamma mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. |
| 2094 | 15179321 | JAK3, a member of JAK kinase family of four (JAK1, JAK2, JAK3 and TYK2), is abundantly expressed in lymphoid cells. |
| 2095 | 15179321 | JAK3 has been found to initiate signaling of interleukin (IL)-2, IL-4, IL-7, IL-9, IL-13 and IL-15. |
| 2096 | 15180473 | In all these autoimmune diseases clinical improvement was associated with the skewing of IFN-gamma producing autoantigen-specific Th1 cells into an IL-4 dominated Th2 phenotype. |
| 2097 | 15180473 | The most powerful cytokines capable of inducing anti-inflammatory Th2 cells are IL-4 itself or IL-11. |
| 2098 | 15180473 | This review focuses on the potential immune deviating strategies based on the use of IL-4, IL-11 or FAE in the therapy of psoriasis, the effects of these agents on the immune system, potential risks and future perspectives for therapeutic intervention by immune deviation replacing immunosuppression. |
| 2099 | 15180473 | In all these autoimmune diseases clinical improvement was associated with the skewing of IFN-gamma producing autoantigen-specific Th1 cells into an IL-4 dominated Th2 phenotype. |
| 2100 | 15180473 | The most powerful cytokines capable of inducing anti-inflammatory Th2 cells are IL-4 itself or IL-11. |
| 2101 | 15180473 | This review focuses on the potential immune deviating strategies based on the use of IL-4, IL-11 or FAE in the therapy of psoriasis, the effects of these agents on the immune system, potential risks and future perspectives for therapeutic intervention by immune deviation replacing immunosuppression. |
| 2102 | 15180473 | In all these autoimmune diseases clinical improvement was associated with the skewing of IFN-gamma producing autoantigen-specific Th1 cells into an IL-4 dominated Th2 phenotype. |
| 2103 | 15180473 | The most powerful cytokines capable of inducing anti-inflammatory Th2 cells are IL-4 itself or IL-11. |
| 2104 | 15180473 | This review focuses on the potential immune deviating strategies based on the use of IL-4, IL-11 or FAE in the therapy of psoriasis, the effects of these agents on the immune system, potential risks and future perspectives for therapeutic intervention by immune deviation replacing immunosuppression. |
| 2105 | 15225820 | After culture with 20 ng/ml GM-CSF + 20 ng/ml IL-4 (8 days) followed by 1000 ng/ml LPS + 100 U/ml IFN-gamma (2 days), with or without 10(-8)M TX527, cells were counted and analyzed by FACS for MHC II, CD86, CD40 and CD54 expression within the CD11c(+) DC population. |
| 2106 | 15225820 | On CD11c(+) DCs, MHC II, CD86 and CD54 were significantly down-regulated and CD40 was twofold upregulated. |
| 2107 | 15233546 | The concentrations of Th1/Th2 related cytokines [interferon (IFN)-gamma, interleukin (IL)-12 vs IL-4, IL-10] in the culture supernatants were measured by ELISA. |
| 2108 | 15233546 | PBMC from patients with GD after treatment produced significantly more IFN-gamma and IL-4 than PBMC from patients with GD before treatment, but there were no significant differences in calculated ratios of Th1 against Th2 cytokines between these two groups. |
| 2109 | 15233546 | When compared to PBMC from healthy controls, PBMC from patients with GD after treatment produced significantly more IL-4 and significantly less IL-12. |
| 2110 | 15233546 | The calculated IL-12/IL-4 ratio after treatment was significantly lower than the same ratio from healthy controls. |
| 2111 | 15233546 | The concentrations of Th1/Th2 related cytokines [interferon (IFN)-gamma, interleukin (IL)-12 vs IL-4, IL-10] in the culture supernatants were measured by ELISA. |
| 2112 | 15233546 | PBMC from patients with GD after treatment produced significantly more IFN-gamma and IL-4 than PBMC from patients with GD before treatment, but there were no significant differences in calculated ratios of Th1 against Th2 cytokines between these two groups. |
| 2113 | 15233546 | When compared to PBMC from healthy controls, PBMC from patients with GD after treatment produced significantly more IL-4 and significantly less IL-12. |
| 2114 | 15233546 | The calculated IL-12/IL-4 ratio after treatment was significantly lower than the same ratio from healthy controls. |
| 2115 | 15233546 | The concentrations of Th1/Th2 related cytokines [interferon (IFN)-gamma, interleukin (IL)-12 vs IL-4, IL-10] in the culture supernatants were measured by ELISA. |
| 2116 | 15233546 | PBMC from patients with GD after treatment produced significantly more IFN-gamma and IL-4 than PBMC from patients with GD before treatment, but there were no significant differences in calculated ratios of Th1 against Th2 cytokines between these two groups. |
| 2117 | 15233546 | When compared to PBMC from healthy controls, PBMC from patients with GD after treatment produced significantly more IL-4 and significantly less IL-12. |
| 2118 | 15233546 | The calculated IL-12/IL-4 ratio after treatment was significantly lower than the same ratio from healthy controls. |
| 2119 | 15233546 | The concentrations of Th1/Th2 related cytokines [interferon (IFN)-gamma, interleukin (IL)-12 vs IL-4, IL-10] in the culture supernatants were measured by ELISA. |
| 2120 | 15233546 | PBMC from patients with GD after treatment produced significantly more IFN-gamma and IL-4 than PBMC from patients with GD before treatment, but there were no significant differences in calculated ratios of Th1 against Th2 cytokines between these two groups. |
| 2121 | 15233546 | When compared to PBMC from healthy controls, PBMC from patients with GD after treatment produced significantly more IL-4 and significantly less IL-12. |
| 2122 | 15233546 | The calculated IL-12/IL-4 ratio after treatment was significantly lower than the same ratio from healthy controls. |
| 2123 | 15236752 | Increased in vivo frequency of IA-2 peptide-reactive IFNgamma+/IL-4- T cells in type 1 diabetic subjects. |
| 2124 | 15236752 | When tested in a high resolution IFNgamma/IL-4 double color ELISPOT assay directly ex vivo, the number of IA-2-reactive IFNgamma producing cells was 17-fold higher in patients than in controls and IL-4 producing cells were not present. |
| 2125 | 15236752 | Increased in vivo frequency of IA-2 peptide-reactive IFNgamma+/IL-4- T cells in type 1 diabetic subjects. |
| 2126 | 15236752 | When tested in a high resolution IFNgamma/IL-4 double color ELISPOT assay directly ex vivo, the number of IA-2-reactive IFNgamma producing cells was 17-fold higher in patients than in controls and IL-4 producing cells were not present. |
| 2127 | 15240727 | The expression of IL-1beta, TNF-alpha, and IL-12 was significantly decreased in the spleen of AG-treated, KRV-infected DR-BB rats compared with PBS-treated, KRV-infected control rats. |
| 2128 | 15240727 | Subsequent experiments revealed that AG treatment exerted its preventive effect in KRV-infected rats by maintaining the finely tuned immune balance normally disrupted by KRV, evidenced by a significant decrease in the expression of IFN-gamma, but not IL-4, and a decrease in Th1-type chemokine receptors CCR5, CXCR3, and CXCR4. |
| 2129 | 15240727 | We also found that iNOS inhibition by AG decreased the KRV-induced expression of MHC class II molecules and IL-2R alpha-chain, resulting in the suppression of T cell activation, evidenced by the decreased cytolytic activity of CD8(+) T cells. |
| 2130 | 15270841 | However, DNA vaccination encoding microbial or reporter antigens is known to induce specific long-lasting CD4 Th1 and strong cytolytic CD8 T cell responses. |
| 2131 | 15270841 | Simultaneously, DNA immunization induced GAD-specific CD4 T cells secreting interleukin (IL)-4 (P < 0.05) and transforming growth factor (TGF)-beta (P = 0.03). |
| 2132 | 15270841 | Furthermore, vaccination produced high amounts of Th2 cytokine-related IgG1 (P < 3.10(-3)) and TGF-beta-related IgG2b to GAD (P = 0.015). |
| 2133 | 15270841 | Surprisingly, diabetes onset was correlated positively with Th2-related GAD-specific IgG1 (P < 10(-4)) and TGF-beta-related IgG2b (P < 3.10(-3)). |
| 2134 | 15322171 | We now show that overexpression in NOD mice of CD1d-restricted TCR Valpha3.2(+)Vbeta9(+) NKT cells producing high levels of IFN-gamma but low amounts of IL-4 leads to prevention of type 1 diabetes, demonstrating a role for nonclassical CD1d-restricted NKT cells in the regulation of autoimmune diabetes. |
| 2135 | 15331543 | Strikingly, host autoreactive T-cells from mice with long-surviving islet grafts predominantly produce interleukin-4, whereas autoreactive T-cells from mice that rejected their islet grafts predominantly produce interferon-gamma. |
| 2136 | 15368281 | While CD4(+) T cells from NOD mice secreted IFN-gamma, IL-4, IL-5 and IL-10 in response to LACK, those from LACK-expressing Tg mice secreted reduced levels of cytokines. |
| 2137 | 15374883 | The prevention of GVHD in those recipients was associated with low-level production of inflammatory cytokines (ie, tumor necrosis factor alpha [TNF-alpha]), high-level production of anti-inflammatory cytokines (ie, interleukin 4 [IL-4] and IL-10), and confining of the donor CD8+ T-cell expansion to lymphohematopoietic tissues. |
| 2138 | 15382512 | [Plasma levels of interleukin-1beta, interleukin-2 and interleukin-4 in recently diagnosed type 1 diabetic children and their association with beta-pancreatic autoantibodies]. |
| 2139 | 15492021 | In vivo apoptosis of diabetogenic T cells in NOD mice by IFN-gamma/TNF-alpha. |
| 2140 | 15492021 | BCG immunization sequentially induced the production of TNF-alpha, IFN-gamma and IL-4 by splenocytes, increased the expression of Fas(high) (Apo-1/CD95), Fas ligand (FasL, CD95L) and TNF receptor (TNFR) on T cells leading to T cell apoptosis. |
| 2141 | 15492021 | The primary role of IFN-gamma and TNF-alpha in BCG-immunotherapy was demonstrated by (i) reversing the immune regulatory effect of BCG by in vivo treatment with neutralizing anti-cytokine antibodies, (ii) inducing effect similar to BCG by treatment with these cytokines. |
| 2142 | 15492021 | We show that Fas and TNF are two pathways in BCG-induced apoptosis of diabetogenic T cells, since in vitro blocking FasL or TNFR1 with antibody reduced T cell apoptosis and increased T cell proliferative response. |
| 2143 | 15492021 | Our results suggest that BCG down-regulates destructive autoimmunity by TNF-alpha/IFN-gamma-induced apoptosis of diabetogenic T cells through both Fas and TNF pathways. |
| 2144 | 15518817 | The failure to observe CVB replication within islets of young NOD mice has been proposed to be due to interferon expression by insulin-producing beta cells or lack of expression of the CVB receptor CAR. |
| 2145 | 15518817 | We found that CAR protein is detectable within islets of young and older NOD mice and that a CVB3 strain, which expresses murine IL-4, can replicate in islets. |
| 2146 | 15542454 | Nonspecific in vitro stimulation induced more CD-4+/IL-4+ cells in Brussels maintained. |
| 2147 | 15542454 | TSHR stimulation produced a significant increase in IL-4 secretion in six of nine local but one of seven Brussels mice. |
| 2148 | 15542454 | Nonspecific in vitro stimulation induced more CD-4+/IL-4+ cells in Brussels maintained. |
| 2149 | 15542454 | TSHR stimulation produced a significant increase in IL-4 secretion in six of nine local but one of seven Brussels mice. |
| 2150 | 15557171 | Immunization of NOD mice with autoantigens such as glutamic acid decarboxylase (GAD) 221-235 peptide (p221) can induce Ag-specific CD4(+) T regulatory (Tr) cells. |
| 2151 | 15557171 | The N221(+) T cells produced IFN-gamma and IL-10, but very little IL-4, in response to p221 stimulation. |
| 2152 | 15557171 | This suppressive activity was cell contact-independent and was abrogated by Abs to IL-10 or IL-10R. |
| 2153 | 15557171 | Interestingly, IL-2 produced by other T cells present in the cell culture induced unactivated N221(+) T cells to exhibit regulatory activities involving production of IL-10. |
| 2154 | 15606614 | In diabetic mice, the levels of IL-12 and IFN-gamma in the lung, liver and spleen were lower than those in control animals on day 14 postinfection, while the opposite was true for IL-4 levels in the lung and liver. |
| 2155 | 15606614 | The expression pattern of inducible nitric oxide synthase (iNOS), in the two mice types was as for IL-12 and IFN-gamma. |
| 2156 | 15613333 | To understand this acceleration and protection process, we challenged 8- and 12-week-old NOD mice containing a disruption in interleukin-4 (IL-4) or gamma interferon (IFN-gamma) genes (NOD IL-4-/- and NOD IFN-gamma-/-, respectively) with a diabetogenic, pancreatropic Edwards strain of CVB4. |
| 2157 | 15613333 | The elimination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the elimination of IFN-gamma delayed these events several weeks. |
| 2158 | 15613333 | CVB4 infection in 8-week-old mice only significantly accelerated the onset of diabetes in a subset of standard, but not IL-4- or IFN-gamma-deficient, NOD mice. |
| 2159 | 15613333 | When mice were infected at 12 weeks of age, the onset of diabetes was accelerated in NOD IL-4-/- mice, while neither acceleration nor long-term protection was elicited in NOD IFN-gamma-/- mice. |
| 2160 | 15613333 | No differences were observed in the kinetics of CVB4 clearance in pancreases from NOD, NOD IL-4-/-, and NOD IFN-gamma-/- mice. |
| 2161 | 15613333 | Collectively, these results suggest that at the insulitis threshold at which CVB4 infection can first accelerate the onset of diabetes in NOD mice, IL-4 as well as IFN-gamma contributes to this pathogenic process. |
| 2162 | 15613333 | The protective mechanism against diabetes elicited in NOD mice infected with CVB4 prior to the development of a critical threshold level of insulitis requires neither IL-4 nor IFN-gamma. |
| 2163 | 15613333 | To understand this acceleration and protection process, we challenged 8- and 12-week-old NOD mice containing a disruption in interleukin-4 (IL-4) or gamma interferon (IFN-gamma) genes (NOD IL-4-/- and NOD IFN-gamma-/-, respectively) with a diabetogenic, pancreatropic Edwards strain of CVB4. |
| 2164 | 15613333 | The elimination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the elimination of IFN-gamma delayed these events several weeks. |
| 2165 | 15613333 | CVB4 infection in 8-week-old mice only significantly accelerated the onset of diabetes in a subset of standard, but not IL-4- or IFN-gamma-deficient, NOD mice. |
| 2166 | 15613333 | When mice were infected at 12 weeks of age, the onset of diabetes was accelerated in NOD IL-4-/- mice, while neither acceleration nor long-term protection was elicited in NOD IFN-gamma-/- mice. |
| 2167 | 15613333 | No differences were observed in the kinetics of CVB4 clearance in pancreases from NOD, NOD IL-4-/-, and NOD IFN-gamma-/- mice. |
| 2168 | 15613333 | Collectively, these results suggest that at the insulitis threshold at which CVB4 infection can first accelerate the onset of diabetes in NOD mice, IL-4 as well as IFN-gamma contributes to this pathogenic process. |
| 2169 | 15613333 | The protective mechanism against diabetes elicited in NOD mice infected with CVB4 prior to the development of a critical threshold level of insulitis requires neither IL-4 nor IFN-gamma. |
| 2170 | 15613333 | To understand this acceleration and protection process, we challenged 8- and 12-week-old NOD mice containing a disruption in interleukin-4 (IL-4) or gamma interferon (IFN-gamma) genes (NOD IL-4-/- and NOD IFN-gamma-/-, respectively) with a diabetogenic, pancreatropic Edwards strain of CVB4. |
| 2171 | 15613333 | The elimination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the elimination of IFN-gamma delayed these events several weeks. |
| 2172 | 15613333 | CVB4 infection in 8-week-old mice only significantly accelerated the onset of diabetes in a subset of standard, but not IL-4- or IFN-gamma-deficient, NOD mice. |
| 2173 | 15613333 | When mice were infected at 12 weeks of age, the onset of diabetes was accelerated in NOD IL-4-/- mice, while neither acceleration nor long-term protection was elicited in NOD IFN-gamma-/- mice. |
| 2174 | 15613333 | No differences were observed in the kinetics of CVB4 clearance in pancreases from NOD, NOD IL-4-/-, and NOD IFN-gamma-/- mice. |
| 2175 | 15613333 | Collectively, these results suggest that at the insulitis threshold at which CVB4 infection can first accelerate the onset of diabetes in NOD mice, IL-4 as well as IFN-gamma contributes to this pathogenic process. |
| 2176 | 15613333 | The protective mechanism against diabetes elicited in NOD mice infected with CVB4 prior to the development of a critical threshold level of insulitis requires neither IL-4 nor IFN-gamma. |
| 2177 | 15613333 | To understand this acceleration and protection process, we challenged 8- and 12-week-old NOD mice containing a disruption in interleukin-4 (IL-4) or gamma interferon (IFN-gamma) genes (NOD IL-4-/- and NOD IFN-gamma-/-, respectively) with a diabetogenic, pancreatropic Edwards strain of CVB4. |
| 2178 | 15613333 | The elimination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the elimination of IFN-gamma delayed these events several weeks. |
| 2179 | 15613333 | CVB4 infection in 8-week-old mice only significantly accelerated the onset of diabetes in a subset of standard, but not IL-4- or IFN-gamma-deficient, NOD mice. |
| 2180 | 15613333 | When mice were infected at 12 weeks of age, the onset of diabetes was accelerated in NOD IL-4-/- mice, while neither acceleration nor long-term protection was elicited in NOD IFN-gamma-/- mice. |
| 2181 | 15613333 | No differences were observed in the kinetics of CVB4 clearance in pancreases from NOD, NOD IL-4-/-, and NOD IFN-gamma-/- mice. |
| 2182 | 15613333 | Collectively, these results suggest that at the insulitis threshold at which CVB4 infection can first accelerate the onset of diabetes in NOD mice, IL-4 as well as IFN-gamma contributes to this pathogenic process. |
| 2183 | 15613333 | The protective mechanism against diabetes elicited in NOD mice infected with CVB4 prior to the development of a critical threshold level of insulitis requires neither IL-4 nor IFN-gamma. |
| 2184 | 15613333 | To understand this acceleration and protection process, we challenged 8- and 12-week-old NOD mice containing a disruption in interleukin-4 (IL-4) or gamma interferon (IFN-gamma) genes (NOD IL-4-/- and NOD IFN-gamma-/-, respectively) with a diabetogenic, pancreatropic Edwards strain of CVB4. |
| 2185 | 15613333 | The elimination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the elimination of IFN-gamma delayed these events several weeks. |
| 2186 | 15613333 | CVB4 infection in 8-week-old mice only significantly accelerated the onset of diabetes in a subset of standard, but not IL-4- or IFN-gamma-deficient, NOD mice. |
| 2187 | 15613333 | When mice were infected at 12 weeks of age, the onset of diabetes was accelerated in NOD IL-4-/- mice, while neither acceleration nor long-term protection was elicited in NOD IFN-gamma-/- mice. |
| 2188 | 15613333 | No differences were observed in the kinetics of CVB4 clearance in pancreases from NOD, NOD IL-4-/-, and NOD IFN-gamma-/- mice. |
| 2189 | 15613333 | Collectively, these results suggest that at the insulitis threshold at which CVB4 infection can first accelerate the onset of diabetes in NOD mice, IL-4 as well as IFN-gamma contributes to this pathogenic process. |
| 2190 | 15613333 | The protective mechanism against diabetes elicited in NOD mice infected with CVB4 prior to the development of a critical threshold level of insulitis requires neither IL-4 nor IFN-gamma. |
| 2191 | 15613333 | To understand this acceleration and protection process, we challenged 8- and 12-week-old NOD mice containing a disruption in interleukin-4 (IL-4) or gamma interferon (IFN-gamma) genes (NOD IL-4-/- and NOD IFN-gamma-/-, respectively) with a diabetogenic, pancreatropic Edwards strain of CVB4. |
| 2192 | 15613333 | The elimination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the elimination of IFN-gamma delayed these events several weeks. |
| 2193 | 15613333 | CVB4 infection in 8-week-old mice only significantly accelerated the onset of diabetes in a subset of standard, but not IL-4- or IFN-gamma-deficient, NOD mice. |
| 2194 | 15613333 | When mice were infected at 12 weeks of age, the onset of diabetes was accelerated in NOD IL-4-/- mice, while neither acceleration nor long-term protection was elicited in NOD IFN-gamma-/- mice. |
| 2195 | 15613333 | No differences were observed in the kinetics of CVB4 clearance in pancreases from NOD, NOD IL-4-/-, and NOD IFN-gamma-/- mice. |
| 2196 | 15613333 | Collectively, these results suggest that at the insulitis threshold at which CVB4 infection can first accelerate the onset of diabetes in NOD mice, IL-4 as well as IFN-gamma contributes to this pathogenic process. |
| 2197 | 15613333 | The protective mechanism against diabetes elicited in NOD mice infected with CVB4 prior to the development of a critical threshold level of insulitis requires neither IL-4 nor IFN-gamma. |
| 2198 | 15613333 | To understand this acceleration and protection process, we challenged 8- and 12-week-old NOD mice containing a disruption in interleukin-4 (IL-4) or gamma interferon (IFN-gamma) genes (NOD IL-4-/- and NOD IFN-gamma-/-, respectively) with a diabetogenic, pancreatropic Edwards strain of CVB4. |
| 2199 | 15613333 | The elimination of IL-4 did not alter the rate of insulitis or diabetes development in NOD mice, while the elimination of IFN-gamma delayed these events several weeks. |
| 2200 | 15613333 | CVB4 infection in 8-week-old mice only significantly accelerated the onset of diabetes in a subset of standard, but not IL-4- or IFN-gamma-deficient, NOD mice. |
| 2201 | 15613333 | When mice were infected at 12 weeks of age, the onset of diabetes was accelerated in NOD IL-4-/- mice, while neither acceleration nor long-term protection was elicited in NOD IFN-gamma-/- mice. |
| 2202 | 15613333 | No differences were observed in the kinetics of CVB4 clearance in pancreases from NOD, NOD IL-4-/-, and NOD IFN-gamma-/- mice. |
| 2203 | 15613333 | Collectively, these results suggest that at the insulitis threshold at which CVB4 infection can first accelerate the onset of diabetes in NOD mice, IL-4 as well as IFN-gamma contributes to this pathogenic process. |
| 2204 | 15613333 | The protective mechanism against diabetes elicited in NOD mice infected with CVB4 prior to the development of a critical threshold level of insulitis requires neither IL-4 nor IFN-gamma. |
| 2205 | 15616624 | The evidence that human insulin-dependent diabetes mellitus (IDDM) is a T cell-mediated disease is well substantiated, and the use of transgenic technology to understand the Th1/Th2 paradigm will provide keys to attenuating pathogenic autoimmunity. |
| 2206 | 15616624 | Insofar as the role of Th1 cytokines in IDDM is concerned, interferon gamma is considered a critical player in the etiology, a proinflammatory role has been determined for IDDM, interleukin-2 is considered an "amplification" factor, and tumor necrosis factor-alpha presents dichotomous effects. |
| 2207 | 15616624 | Regarding the role of Th2 cytokines in IDDM, interleukin-4 is essential for immunoprotection and counterregulation of IDDM, and interleukin-10 plays immunoprotective and destructive roles. |
| 2208 | 15616624 | Of all the cytokines examined, IL-4 seems to be the likely candidate for preventing IDDM. |
| 2209 | 15616624 | The evidence that human insulin-dependent diabetes mellitus (IDDM) is a T cell-mediated disease is well substantiated, and the use of transgenic technology to understand the Th1/Th2 paradigm will provide keys to attenuating pathogenic autoimmunity. |
| 2210 | 15616624 | Insofar as the role of Th1 cytokines in IDDM is concerned, interferon gamma is considered a critical player in the etiology, a proinflammatory role has been determined for IDDM, interleukin-2 is considered an "amplification" factor, and tumor necrosis factor-alpha presents dichotomous effects. |
| 2211 | 15616624 | Regarding the role of Th2 cytokines in IDDM, interleukin-4 is essential for immunoprotection and counterregulation of IDDM, and interleukin-10 plays immunoprotective and destructive roles. |
| 2212 | 15616624 | Of all the cytokines examined, IL-4 seems to be the likely candidate for preventing IDDM. |
| 2213 | 15621575 | Insulin-like growth factor-1 (IGF-1)-derived peptide protects against diabetes in NOD mice. |
| 2214 | 15621575 | Here, we report the significance of insulin-like growth factor-1 (IGF-1) peptide as a tool for the prevention of type 1 diabetes. |
| 2215 | 15621575 | Female NOD mice were immunized with a subcutaneous injection of IGF-1, glutamic acid decarboxylase (GAD), insulin or IGF-1-derived peptides (residues 8-23, 24-41 or 50-70) in incomplete Freund's adjuvant (IFA) or with IFA only as the control group at 4 weeks of age, and observed up to 36-37 weeks of age. |
| 2216 | 15621575 | Diabetes onset was significantly suppressed and delayed in the IGF-1 group as compared to the GAD, insulin and control groups (p<0.05), and it was significantly suppressed and delayed in the (50-70)IGF-1 group as compared to the (8-23)IGF-1 and control groups (p<0.02). |
| 2217 | 15621575 | Although the degree of insulitis in all treated mice was not significantly different, a significant number of IL-4-producing cells in response to IGF-1 peptides were detected in (50-70)IGF-1-treated mice in intracellular cytokine assay. |
| 2218 | 15660293 | No evidence of association or interaction between the IL4RA, IL4, and IL13 genes in type 1 diabetes. |
| 2219 | 15660293 | Gene-gene interaction, albeit only marginally significant, has recently been reported for the interleukin-4 and interleukin-13 genes (IL4 and IL13) with the interleukin-4 receptor A gene (IL4RA), contributing to the susceptibility of type 1 diabetes (T1D). |
| 2220 | 15660293 | No evidence of association or interaction between the IL4RA, IL4, and IL13 genes in type 1 diabetes. |
| 2221 | 15660293 | Gene-gene interaction, albeit only marginally significant, has recently been reported for the interleukin-4 and interleukin-13 genes (IL4 and IL13) with the interleukin-4 receptor A gene (IL4RA), contributing to the susceptibility of type 1 diabetes (T1D). |
| 2222 | 15667574 | Aberrant regulation of interleukin-12 receptor beta2 chain on type 1 cytokine-stimulated T lymphocytes in type 1 diabetes. |
| 2223 | 15667574 | We studied, in T1D, type 1 and 2 cytokine-induced expression of the interleukin-12 receptor beta2 chain (IL-12Rbeta2 chain), which plays a critical role in regulating T-cell polarization. |
| 2224 | 15667574 | Peripheral blood lymphocytes from children with newly diagnosed T1D (n=10; mean age 10 years), from children with longstanding T1D (n=8; mean age 12.9 years) and from healthy children (n=15; mean age 11.5 years) were stimulated with phytohaemagglutinin (PHA) in a type 1 (IL-12 and anti-IL-4) or a type 2 (IL-4 and anti-IL-12) cytokine environment. |
| 2225 | 15667574 | Secretion of interferon-gamma (IFN-gamma), IL-5 and IL-13, as detected by enzyme-linked immunosorbent assay (ELISA), and expression of the IL-12Rbeta2 chain on CD4 and CD8 cells by flow cytometry, were analysed. |
| 2226 | 15667574 | Children with newly diagnosed and longstanding T1D had lower expression levels of the IL-12Rbeta2 chain on IL-12Rbeta2 chain-positive CD4 T cells (for a type 1 or a type 2 cytokine environment: P=0.01 and P=0.002 or P=0.02 and P=0.01, respectively) and on IL-12Rbeta2 chain-positive CD8 T cells (for a type 1 or a type 2 cytokine environment: P=0.007 and P=0.0007 or P=0.003 and P=0.01, respectively) when compared to healthy children. |
| 2227 | 15667574 | A decreased percentage of IL-12Rbeta2 chain-expressing CD4 T cells (P=0.07 and P=0.03) and CD8 T cells (P=0.004 and P=0.01) and increased secretion of IL-13 (P=0.006 and P=0.04) in a type 1 cytokine environment was seen in both groups of patients. |
| 2228 | 15677345 | Biochemical analysis of the pancreas showed that OGG-1(-/-) mice had greater insulin content, indicative of a greater beta-cell mass coupled with lower levels of the chemokine MIP-1alpha and Th1 cytokines IL-12 and TNF-alpha. |
| 2229 | 15677345 | Levels of protective Th2 cytokines, IL-4 and IL-10 were significantly higher in the pancreata of OGG-1(-/-) mice as compared with the levels measured in wild-type mice. |
| 2230 | 15683454 | Using the sensitive enzyme-linked immunospot (ELISPOT) technique to divide Th1- from Th2-like lymphocytes, secretion of interferon-gamma (IFN-gamma) and interleukin-4 was analysed from lymphocytes spontaneously and after in vitro stimulation with different antigens, based on present paradigms regarding the pathogenesis of type 1 diabetes. |
| 2231 | 15683454 | Compared to the response observed in healthy individuals, we found that individuals with a high risk of developing type 1 diabetes, especially children, responded with less IFN-gamma secretion to the three autoantigens glutamic acid decarboxylase 65 (GAD65), insulin and tyrosinphosphatase (IA-2). |
| 2232 | 15699123 | These experiments reveal that cytokines such as IL-4, IL-10, IL-13, and TGF-beta, that have been involved in other functions of NKT cells, play only a minor role if any in the blockade of T cell differentiation by NKT cells. |
| 2233 | 15699123 | Diabetes is still prevented by NKT cells in the absence of functional IL-4, IL-10, IL-13, and TGF-beta. |
| 2234 | 15699123 | These experiments reveal that cytokines such as IL-4, IL-10, IL-13, and TGF-beta, that have been involved in other functions of NKT cells, play only a minor role if any in the blockade of T cell differentiation by NKT cells. |
| 2235 | 15699123 | Diabetes is still prevented by NKT cells in the absence of functional IL-4, IL-10, IL-13, and TGF-beta. |
| 2236 | 15699493 | An insulin-like growth factor 2-derived self-antigen inducing a regulatory cytokine profile after presentation to peripheral blood mononuclear cells from DQ8+ type 1 diabetic adolescents: preliminary design of a thymus-based tolerogenic self-vaccination. |
| 2237 | 15699493 | This work aims to evaluate the potential use of insulin-like growth factor 2 (IGF-2) as the dominant thymic self-antigen precursor of the insulin family in designing a tolerogenic approach to type 1 diabetes (T1D) prevention. |
| 2238 | 15699493 | This evaluation was primarily based on cytokine profile driven by MHC presentation of insulin and IGF-2-derived antigens to PBMC cultures derived from 16 T1D DQ8(+) adolescents. |
| 2239 | 15699493 | Insulin B9-23, one dominant beta-cell autoantigen, and the homologous sequence B11-25 of IGF-2 display the same affinity and fully compete for binding to DQ8, a MHC-II allele conferring major genetic susceptibility to type 1 diabetes (T1D). |
| 2240 | 15699493 | However, compared to insulin B9-23, presentation of IGF-2 B11-25 elicits a suppressive/regulatory cytokine profile with a higher number of IL-10-secreting cells (P < 0.05), a much higher ratio of IL-10/IFN-gamma (P < 0.01), as well as a lower number of IL-4-secreting cells (P < 0.05). |
| 2241 | 15734555 | IL-4, IL-10). |
| 2242 | 15734555 | Proposed antigens such as insulin, glutamic acid decarboxilase (GAD) and the heat shock protein 60 (Hsp60)-derived peptide 277 have been used successfully in murine diabetes models and in initial clinical trials in early diabetes patients. |
| 2243 | 15814672 | Tolerance induction of autoreactive T cells against pancreatic beta cell-specific autoantigens such as glutamic acid decarboxylase 65 (GAD65) and insulin has been attempted as a method to prevent autoimmune diabetes. |
| 2244 | 15814672 | In this study, we investigate whether adenoassociated virus (AAV) gene delivery of multiple immunodominant epitopes expressing GAD(500-585) could induce potent immune tolerance and persistently suppress autoimmune diabetes in NOD mice. |
| 2245 | 15814672 | This prevention was marked by the inactivation of GAD(500-585)-responsive T lymphocytes, the enhanced GAD(500-585)-specific Th2 response (characterized by increased IL-4, IL-10 production, and decreased IFN-gamma production; especially elevated anti-GAD(500-585) IgG1 titer; and relatively unchanged anti-GAD(500-585) IgG2b titer), the increased secretion of TGF-beta, and the production of protective regulatory cells. |
| 2246 | 15814672 | These data indicate that using AAV, a vector with advantage for therapeutic gene delivery, to transfer autoantigen peptide GAD(500-585), can induce immunological tolerance through active suppression of effector T cells and prevent type I diabetes in NOD mice. |
| 2247 | 15832295 | Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter. |
| 2248 | 15832295 | NOD CD8(+) T cells had an increased propensity to produce IFN-gamma upon TCR activation, in both adult and 2-week-old mice. |
| 2249 | 15832295 | NOD CD8(+) T cells had a reduced capacity to produce IL-4 in type 2 conditions compared to CD8(+) T cells from the diabetes-resistant strains BALB/c and C57BL/6. |
| 2250 | 15832295 | Both GATA-3 and c-Maf, two positive transactivators for IL-4 gene expression, were expressed in type 2 conditions at comparable levels in NOD CD8(+) T cells. |
| 2251 | 15832295 | The GATA-3 was functional since normal levels of IL-5 were produced and the IL-4 promoter was hyperacetylated in NOD CD8(+) T cells. |
| 2252 | 15832295 | These results suggest that NOD CD8(+) T cells possess an increased propensity to produce IFN-gamma and impaired c-Maf-dependent DNA binding activities in vivo that lead to reduced IL-4 production following TCR activation. |
| 2253 | 15832295 | Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter. |
| 2254 | 15832295 | NOD CD8(+) T cells had an increased propensity to produce IFN-gamma upon TCR activation, in both adult and 2-week-old mice. |
| 2255 | 15832295 | NOD CD8(+) T cells had a reduced capacity to produce IL-4 in type 2 conditions compared to CD8(+) T cells from the diabetes-resistant strains BALB/c and C57BL/6. |
| 2256 | 15832295 | Both GATA-3 and c-Maf, two positive transactivators for IL-4 gene expression, were expressed in type 2 conditions at comparable levels in NOD CD8(+) T cells. |
| 2257 | 15832295 | The GATA-3 was functional since normal levels of IL-5 were produced and the IL-4 promoter was hyperacetylated in NOD CD8(+) T cells. |
| 2258 | 15832295 | These results suggest that NOD CD8(+) T cells possess an increased propensity to produce IFN-gamma and impaired c-Maf-dependent DNA binding activities in vivo that lead to reduced IL-4 production following TCR activation. |
| 2259 | 15832295 | Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter. |
| 2260 | 15832295 | NOD CD8(+) T cells had an increased propensity to produce IFN-gamma upon TCR activation, in both adult and 2-week-old mice. |
| 2261 | 15832295 | NOD CD8(+) T cells had a reduced capacity to produce IL-4 in type 2 conditions compared to CD8(+) T cells from the diabetes-resistant strains BALB/c and C57BL/6. |
| 2262 | 15832295 | Both GATA-3 and c-Maf, two positive transactivators for IL-4 gene expression, were expressed in type 2 conditions at comparable levels in NOD CD8(+) T cells. |
| 2263 | 15832295 | The GATA-3 was functional since normal levels of IL-5 were produced and the IL-4 promoter was hyperacetylated in NOD CD8(+) T cells. |
| 2264 | 15832295 | These results suggest that NOD CD8(+) T cells possess an increased propensity to produce IFN-gamma and impaired c-Maf-dependent DNA binding activities in vivo that lead to reduced IL-4 production following TCR activation. |
| 2265 | 15832295 | Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter. |
| 2266 | 15832295 | NOD CD8(+) T cells had an increased propensity to produce IFN-gamma upon TCR activation, in both adult and 2-week-old mice. |
| 2267 | 15832295 | NOD CD8(+) T cells had a reduced capacity to produce IL-4 in type 2 conditions compared to CD8(+) T cells from the diabetes-resistant strains BALB/c and C57BL/6. |
| 2268 | 15832295 | Both GATA-3 and c-Maf, two positive transactivators for IL-4 gene expression, were expressed in type 2 conditions at comparable levels in NOD CD8(+) T cells. |
| 2269 | 15832295 | The GATA-3 was functional since normal levels of IL-5 were produced and the IL-4 promoter was hyperacetylated in NOD CD8(+) T cells. |
| 2270 | 15832295 | These results suggest that NOD CD8(+) T cells possess an increased propensity to produce IFN-gamma and impaired c-Maf-dependent DNA binding activities in vivo that lead to reduced IL-4 production following TCR activation. |
| 2271 | 15832295 | Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter. |
| 2272 | 15832295 | NOD CD8(+) T cells had an increased propensity to produce IFN-gamma upon TCR activation, in both adult and 2-week-old mice. |
| 2273 | 15832295 | NOD CD8(+) T cells had a reduced capacity to produce IL-4 in type 2 conditions compared to CD8(+) T cells from the diabetes-resistant strains BALB/c and C57BL/6. |
| 2274 | 15832295 | Both GATA-3 and c-Maf, two positive transactivators for IL-4 gene expression, were expressed in type 2 conditions at comparable levels in NOD CD8(+) T cells. |
| 2275 | 15832295 | The GATA-3 was functional since normal levels of IL-5 were produced and the IL-4 promoter was hyperacetylated in NOD CD8(+) T cells. |
| 2276 | 15832295 | These results suggest that NOD CD8(+) T cells possess an increased propensity to produce IFN-gamma and impaired c-Maf-dependent DNA binding activities in vivo that lead to reduced IL-4 production following TCR activation. |
| 2277 | 15833265 | Most NKT cells express both an invariant T cell antigen receptor and the NK cell receptor NK1.1, and are referred to as invariant NKT cells. |
| 2278 | 15833265 | This invariant T cell receptor is restricted to interactions with glycolipids presented by the non-classical MHC, CD1d. |
| 2279 | 15833265 | These NKT cells rapidly produce high levels of interleukin (IL)-2, IFN-gamma, TNF-alpha, and IL-4 upon stimulation through their TCR. |
| 2280 | 15847799 | Media supplemented with IL-2+IL-4 supported growth of the largest number of antigen-specific clones. |
| 2281 | 15847799 | Based on these findings, IL-2+IL-4, anti-CD3 and round-bottom plates were used to clone FACS-sorted autoantigen-specific CFSE-labelled CD4+ T cells. |
| 2282 | 15847799 | Media supplemented with IL-2+IL-4 supported growth of the largest number of antigen-specific clones. |
| 2283 | 15847799 | Based on these findings, IL-2+IL-4, anti-CD3 and round-bottom plates were used to clone FACS-sorted autoantigen-specific CFSE-labelled CD4+ T cells. |
| 2284 | 15864741 | We next showed that Th2 cytokines (IL-4 and/or IL-5) increased but Th1 cytokine (IFN-gamma) decreased following injections with the butanol fraction of B.pilosa in both mouse strains. |
| 2285 | 15867147 | The c-Jun NH(2)-terminal kinase isoform (JNK) 1 is implicated in type 2 diabetes. |
| 2286 | 15867147 | Here, we demonstrate that JNK2 may play an important role in type 1 (insulin-dependent) diabetes that is caused by autoimmune destruction of beta cells. |
| 2287 | 15867147 | CD4(+) T cells from JNK2-deficient nonobese diabetic mice produced less IFN-gamma but significantly increased amounts of IL-4 and IL-5, indicating polarization toward the Th2 phenotype. |
| 2288 | 15867147 | We conclude that JNK protein kinases may have important roles in diabetes, including functions of JNK1 in type 2 diabetes and JNK2 in type 1 diabetes. |
| 2289 | 15870028 | Using IFN-gamma/IL-4 double color ELISPOT, we tested longitudinally the reactivity of PBMC from HLA-matched diabetic patients and healthy controls to GAD65, IA-2, and proinsulin peptides ex vivo and after in vitro culture. |
| 2290 | 15870028 | During in vitro culture, both IFN-gamma- and IL-4-producing cells were induced in controls, suggesting that the precursor cells were uncommitted naive T cells in vivo. |
| 2291 | 15870028 | Using IFN-gamma/IL-4 double color ELISPOT, we tested longitudinally the reactivity of PBMC from HLA-matched diabetic patients and healthy controls to GAD65, IA-2, and proinsulin peptides ex vivo and after in vitro culture. |
| 2292 | 15870028 | During in vitro culture, both IFN-gamma- and IL-4-producing cells were induced in controls, suggesting that the precursor cells were uncommitted naive T cells in vivo. |
| 2293 | 15927845 | We characterized the peak levels, secretory pattern and total cytokine production of the Th1 cytokines (IL-2 and IFN gamma) and Th2 cytokines (IL-4 and IL-10), by stimulated peripheral blood mononuclear cells of twenty six first-degree relatives of T1DM patients, and eleven matched controls. |
| 2294 | 15927845 | At enrollment, first degree relatives demonstrated a significant increase in peak and overall secretion of IL-2; P<0.01 and P<0.005 respectively and IL-4 cytokine; P<0.05 and P<0.01 respectively, as compared to normal controls. |
| 2295 | 15927845 | Their mean IFN gamma secretion increased significantly, P<0.05, after one year while their higher IL-2 and IL-4 secretion remained unchanged. |
| 2296 | 15927845 | Four relatives all Ab positive, developed diabetes: Peak IL-4 levels were low in three and markedly decreased within one year in one of these relatives, while peak IL-2 and IFN gamma levels were elevated in all of them. |
| 2297 | 15927845 | The presence of low IL-4 and elevated IL-2 and IFN gamma levels in autoAb positive relatives is associated with progression to overt disease. |
| 2298 | 15927845 | We characterized the peak levels, secretory pattern and total cytokine production of the Th1 cytokines (IL-2 and IFN gamma) and Th2 cytokines (IL-4 and IL-10), by stimulated peripheral blood mononuclear cells of twenty six first-degree relatives of T1DM patients, and eleven matched controls. |
| 2299 | 15927845 | At enrollment, first degree relatives demonstrated a significant increase in peak and overall secretion of IL-2; P<0.01 and P<0.005 respectively and IL-4 cytokine; P<0.05 and P<0.01 respectively, as compared to normal controls. |
| 2300 | 15927845 | Their mean IFN gamma secretion increased significantly, P<0.05, after one year while their higher IL-2 and IL-4 secretion remained unchanged. |
| 2301 | 15927845 | Four relatives all Ab positive, developed diabetes: Peak IL-4 levels were low in three and markedly decreased within one year in one of these relatives, while peak IL-2 and IFN gamma levels were elevated in all of them. |
| 2302 | 15927845 | The presence of low IL-4 and elevated IL-2 and IFN gamma levels in autoAb positive relatives is associated with progression to overt disease. |
| 2303 | 15927845 | We characterized the peak levels, secretory pattern and total cytokine production of the Th1 cytokines (IL-2 and IFN gamma) and Th2 cytokines (IL-4 and IL-10), by stimulated peripheral blood mononuclear cells of twenty six first-degree relatives of T1DM patients, and eleven matched controls. |
| 2304 | 15927845 | At enrollment, first degree relatives demonstrated a significant increase in peak and overall secretion of IL-2; P<0.01 and P<0.005 respectively and IL-4 cytokine; P<0.05 and P<0.01 respectively, as compared to normal controls. |
| 2305 | 15927845 | Their mean IFN gamma secretion increased significantly, P<0.05, after one year while their higher IL-2 and IL-4 secretion remained unchanged. |
| 2306 | 15927845 | Four relatives all Ab positive, developed diabetes: Peak IL-4 levels were low in three and markedly decreased within one year in one of these relatives, while peak IL-2 and IFN gamma levels were elevated in all of them. |
| 2307 | 15927845 | The presence of low IL-4 and elevated IL-2 and IFN gamma levels in autoAb positive relatives is associated with progression to overt disease. |
| 2308 | 15927845 | We characterized the peak levels, secretory pattern and total cytokine production of the Th1 cytokines (IL-2 and IFN gamma) and Th2 cytokines (IL-4 and IL-10), by stimulated peripheral blood mononuclear cells of twenty six first-degree relatives of T1DM patients, and eleven matched controls. |
| 2309 | 15927845 | At enrollment, first degree relatives demonstrated a significant increase in peak and overall secretion of IL-2; P<0.01 and P<0.005 respectively and IL-4 cytokine; P<0.05 and P<0.01 respectively, as compared to normal controls. |
| 2310 | 15927845 | Their mean IFN gamma secretion increased significantly, P<0.05, after one year while their higher IL-2 and IL-4 secretion remained unchanged. |
| 2311 | 15927845 | Four relatives all Ab positive, developed diabetes: Peak IL-4 levels were low in three and markedly decreased within one year in one of these relatives, while peak IL-2 and IFN gamma levels were elevated in all of them. |
| 2312 | 15927845 | The presence of low IL-4 and elevated IL-2 and IFN gamma levels in autoAb positive relatives is associated with progression to overt disease. |
| 2313 | 15927845 | We characterized the peak levels, secretory pattern and total cytokine production of the Th1 cytokines (IL-2 and IFN gamma) and Th2 cytokines (IL-4 and IL-10), by stimulated peripheral blood mononuclear cells of twenty six first-degree relatives of T1DM patients, and eleven matched controls. |
| 2314 | 15927845 | At enrollment, first degree relatives demonstrated a significant increase in peak and overall secretion of IL-2; P<0.01 and P<0.005 respectively and IL-4 cytokine; P<0.05 and P<0.01 respectively, as compared to normal controls. |
| 2315 | 15927845 | Their mean IFN gamma secretion increased significantly, P<0.05, after one year while their higher IL-2 and IL-4 secretion remained unchanged. |
| 2316 | 15927845 | Four relatives all Ab positive, developed diabetes: Peak IL-4 levels were low in three and markedly decreased within one year in one of these relatives, while peak IL-2 and IFN gamma levels were elevated in all of them. |
| 2317 | 15927845 | The presence of low IL-4 and elevated IL-2 and IFN gamma levels in autoAb positive relatives is associated with progression to overt disease. |
| 2318 | 15944310 | Lack of chemokine receptor CCR5 promotes murine fulminant liver failure by preventing the apoptosis of activated CD1d-restricted NKT cells. |
| 2319 | 15944310 | In this study, we demonstrate that CCR5 deficiency promotes the development of acute FLF in mice following Con A administration by preventing activated hepatic CD1d-restricted NKT cells (but not conventional T cells) from dying from activation-induced apoptosis. |
| 2320 | 15944310 | The resistance of CCR5-deficient NKT cells from activation-induced apoptosis following Con A administration is not due to a defective Fas-driven death pathway. |
| 2321 | 15944310 | Moreover, FLF in CCR5-deficient mice also correlated with hepatic CCR5-deficient NKT cells, producing more IL-4, but not IFN-gamma, relative to wild-type NKT cells. |
| 2322 | 15959781 | Lamina propria (LP) mononuclear cells from helminth-colonized mice make less interleukin (IL)-12 p40 and IFN-gamma, but more IL-4, IL-13, IL-10, TGF-beta, and PGE(2) compared to LP mononuclear cells from naive mice. |
| 2323 | 15988804 | In the second study, the amounts of IFN gamma and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. |
| 2324 | 15988804 | The productions of IFN gamma and IL-4 were detected only in the K and D type CpG ODN administration groups. |
| 2325 | 15988804 | In the second study, the amounts of IFN gamma and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. |
| 2326 | 15988804 | The productions of IFN gamma and IL-4 were detected only in the K and D type CpG ODN administration groups. |
| 2327 | 16002993 | Ubiquitin-protein ligase Cbl-b negatively regulates high affinity IgE receptor (FcepsilonRI)-mediated degranulation and cytokine gene transcription in mast cells. |
| 2328 | 16002993 | FcepsilonRI-mediated tyrosine phosphorylation of Syk, Gab2, and phospholipase C-gamma1, and activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAP kinase), and inhibitor of nuclear factor kappaB kinase (IKK), and generation of Rac1 are unaffected in cells overexpressing the truncated Cbl-b in the lipid raft. |
| 2329 | 16002993 | On the other hand, FcepsilonRI-mediated transcriptional activation of nuclear factor of activated T cells (NFAT), and transcription of interleukin-3 (IL-3) and IL-4 mRNA are inhibited by overexpression of the truncated variant of Cbl-b. |
| 2330 | 16002993 | These structural and functional analyses reveal the mechanism underlying the selective inhibition of cellular signaling by the truncated variant of Cbl-b related to insulin-dependent diabetes mellitus. |
| 2331 | 16046318 | We evaluated associations between candidate genes outside the HLA region-INS, cytotoxic T-lymphocyte-associated antigen (CTLA)-4, interleukin (IL)-4, IL-4R, and IL-13 and islet autoimmunity among children participating in the Diabetes Autoimmunity Study in the Young (DAISY). |
| 2332 | 16046318 | Associations were found between both IL-4R haplotypes and IL-4-IL-13 haplotypes and persistent islet autoimmunity and type 1 diabetes. |
| 2333 | 16046318 | This study confirms the association between the INS and CTLA-4 loci and type 1 diabetes. |
| 2334 | 16046318 | Genes involved in the IL-4 regulatory pathway (IL-4, IL-4R, IL-13) may confer susceptibility or protection to type 1 diabetes depending on individual SNPs or specific haplotypes. |
| 2335 | 16046318 | We evaluated associations between candidate genes outside the HLA region-INS, cytotoxic T-lymphocyte-associated antigen (CTLA)-4, interleukin (IL)-4, IL-4R, and IL-13 and islet autoimmunity among children participating in the Diabetes Autoimmunity Study in the Young (DAISY). |
| 2336 | 16046318 | Associations were found between both IL-4R haplotypes and IL-4-IL-13 haplotypes and persistent islet autoimmunity and type 1 diabetes. |
| 2337 | 16046318 | This study confirms the association between the INS and CTLA-4 loci and type 1 diabetes. |
| 2338 | 16046318 | Genes involved in the IL-4 regulatory pathway (IL-4, IL-4R, IL-13) may confer susceptibility or protection to type 1 diabetes depending on individual SNPs or specific haplotypes. |
| 2339 | 16046318 | We evaluated associations between candidate genes outside the HLA region-INS, cytotoxic T-lymphocyte-associated antigen (CTLA)-4, interleukin (IL)-4, IL-4R, and IL-13 and islet autoimmunity among children participating in the Diabetes Autoimmunity Study in the Young (DAISY). |
| 2340 | 16046318 | Associations were found between both IL-4R haplotypes and IL-4-IL-13 haplotypes and persistent islet autoimmunity and type 1 diabetes. |
| 2341 | 16046318 | This study confirms the association between the INS and CTLA-4 loci and type 1 diabetes. |
| 2342 | 16046318 | Genes involved in the IL-4 regulatory pathway (IL-4, IL-4R, IL-13) may confer susceptibility or protection to type 1 diabetes depending on individual SNPs or specific haplotypes. |
| 2343 | 16048553 | Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. |
| 2344 | 16048553 | Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. |
| 2345 | 16048553 | Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. |
| 2346 | 16048553 | Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. |
| 2347 | 16118326 | In mouse models of virus infection and virus-induced autoimmunity, we tested how heterologous serum affects the immunomodulatory capacity of immature DCs generated in the presence of IL-10 by comparing fetal bovine serum (FBS)- or normal mouse serum (NMS)-supplemented DC cultures. |
| 2348 | 16118326 | We show that FBS-exposed DCs induce a systemic immune deviation characterized by reduction of virus-specific T cells, delayed viral clearance, and enhanced systemic production of interleukin 4 (IL-4), IL-5, and IL-10 to FBS-derived antigens, including bovine serum albumin (BSA). |
| 2349 | 16118326 | These cells did not induce systemic IL-4, IL-5, or IL-10 production and inhibited generation of virus-specific T cells or autoimmunity only if pulsed with a viral antigen. |
| 2350 | 16118326 | In mouse models of virus infection and virus-induced autoimmunity, we tested how heterologous serum affects the immunomodulatory capacity of immature DCs generated in the presence of IL-10 by comparing fetal bovine serum (FBS)- or normal mouse serum (NMS)-supplemented DC cultures. |
| 2351 | 16118326 | We show that FBS-exposed DCs induce a systemic immune deviation characterized by reduction of virus-specific T cells, delayed viral clearance, and enhanced systemic production of interleukin 4 (IL-4), IL-5, and IL-10 to FBS-derived antigens, including bovine serum albumin (BSA). |
| 2352 | 16118326 | These cells did not induce systemic IL-4, IL-5, or IL-10 production and inhibited generation of virus-specific T cells or autoimmunity only if pulsed with a viral antigen. |
| 2353 | 16148057 | Expression of IFN-gamma and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-gamma, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). |
| 2354 | 16148057 | Thus, the ratio of IFN-gamma/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD65 was reduced after treatment in the photopheresis group. |
| 2355 | 16148057 | The IFN-gamma/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. |
| 2356 | 16148057 | Expression of IFN-gamma and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-gamma, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). |
| 2357 | 16148057 | Thus, the ratio of IFN-gamma/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD65 was reduced after treatment in the photopheresis group. |
| 2358 | 16148057 | The IFN-gamma/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. |
| 2359 | 16148057 | Expression of IFN-gamma and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-gamma, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). |
| 2360 | 16148057 | Thus, the ratio of IFN-gamma/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD65 was reduced after treatment in the photopheresis group. |
| 2361 | 16148057 | The IFN-gamma/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. |
| 2362 | 16177088 | From 451 T cell clones from control and diabetic PLN, we derived 55 iNKT cells by two methods and analyzed function by cytokine secretion. iNKT cell clones isolated from control PLN secreted IL-4 and IFN-gamma upon TCR stimulation. |
| 2363 | 16177088 | For type 1a diabetic subjects, PLN iNKT cell clones from three samples secreted IFN-gamma and no IL-4. |
| 2364 | 16177088 | From normal and diabetic PLN, one-third of CD1d tetramer+-sorted T cell clones were reactive with CD1d transfectants or proliferated/secreted cytokine in response to alpha-galactosylceramide-pulsed PBMCs; tetramer-staining T cell clones from diabetic PLN did not secrete IL-4. |
| 2365 | 16177088 | From 451 T cell clones from control and diabetic PLN, we derived 55 iNKT cells by two methods and analyzed function by cytokine secretion. iNKT cell clones isolated from control PLN secreted IL-4 and IFN-gamma upon TCR stimulation. |
| 2366 | 16177088 | For type 1a diabetic subjects, PLN iNKT cell clones from three samples secreted IFN-gamma and no IL-4. |
| 2367 | 16177088 | From normal and diabetic PLN, one-third of CD1d tetramer+-sorted T cell clones were reactive with CD1d transfectants or proliferated/secreted cytokine in response to alpha-galactosylceramide-pulsed PBMCs; tetramer-staining T cell clones from diabetic PLN did not secrete IL-4. |
| 2368 | 16177088 | From 451 T cell clones from control and diabetic PLN, we derived 55 iNKT cells by two methods and analyzed function by cytokine secretion. iNKT cell clones isolated from control PLN secreted IL-4 and IFN-gamma upon TCR stimulation. |
| 2369 | 16177088 | For type 1a diabetic subjects, PLN iNKT cell clones from three samples secreted IFN-gamma and no IL-4. |
| 2370 | 16177088 | From normal and diabetic PLN, one-third of CD1d tetramer+-sorted T cell clones were reactive with CD1d transfectants or proliferated/secreted cytokine in response to alpha-galactosylceramide-pulsed PBMCs; tetramer-staining T cell clones from diabetic PLN did not secrete IL-4. |
| 2371 | 16178791 | Unlike conventional T cells that recognize peptides in association with major histocompatibility complex (MHC), NKT cells recognize glycolipid antigens presented by the non-polymorphic MHC class I-like protein, CD1d. |
| 2372 | 16178791 | Recently, we and other groups have demonstrated that administration of glycolipid ligands such as alpha-galactosylceramide (alpha-GC ) or its sphingosine truncated derivative, OCH suppressed autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), diabetes in NOD mice and collagen-induced arthritis (CIA) by inducing T helper (Th) 2 bias of autoimmune T cells. |
| 2373 | 16178791 | OCH is a unique ligand to stimulate NKT cells to selectively produce Th2 cytokines whereas alpha-GC induces both interleukin (IL)-4 and interferon (IFN)-gamma, and is more beneficial for treatment of a wide variety of Th1-mediated autoimmune diseases. |
| 2374 | 16192669 | The OMp showed reduced TNF-alpha, IL-12, and NO production as well as defective phagocytosis activity compared to nondiabetic controls; however, there was no significant difference with IL-6 production. |
| 2375 | 16192669 | On the other hand, the levels of IFN-gamma or IL-4 of splenocytes in diabetic mice were significantly higher compared to the control mice. |
| 2376 | 16192669 | The ratio of IFN-gamma to IL-4 was also higher at the early stage of diabetes and then declined several weeks later after the occurrence of diabetes, suggesting a pathogenetic TH1 phenotype from the beginning gradually to a tendency of TH2 during the development of diabetes. |
| 2377 | 16192669 | The OMp showed reduced TNF-alpha, IL-12, and NO production as well as defective phagocytosis activity compared to nondiabetic controls; however, there was no significant difference with IL-6 production. |
| 2378 | 16192669 | On the other hand, the levels of IFN-gamma or IL-4 of splenocytes in diabetic mice were significantly higher compared to the control mice. |
| 2379 | 16192669 | The ratio of IFN-gamma to IL-4 was also higher at the early stage of diabetes and then declined several weeks later after the occurrence of diabetes, suggesting a pathogenetic TH1 phenotype from the beginning gradually to a tendency of TH2 during the development of diabetes. |
| 2380 | 16232222 | Mature DC (mDC) from 18 children with T1DM and 10 age-matched healthy children were tested. mDC, derived from peripheral blood monocytes cultured for 6 days in presence of interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) and stimulated with lipopolysaccharide (LPS) for the last 24 h, were phenotyped for the expression of the co-stimulatory molecules B7.1 and B7.2. |
| 2381 | 16232222 | We also measured IL-10 and IL-12 concentration in the supernatant of DC cultures. |
| 2382 | 16232222 | Interestingly, we observed in the patients a sevenfold higher level of IL-10 (P = 0.07) and a ninefold lower level of IL-12 (P = 0.01). |
| 2383 | 16304639 | We investigated whether iNKT activation with alpha-GalCer was protective in collagen-induced arthritis (CIA) in DBA/1 mice, a standard model of rheumatoid arthritis. |
| 2384 | 16304639 | Here, we have shown that in vivo iNKT cell function was altered in DBA/1 mice since stimulation with alpha-GalCer led to decreased IL-4 and IFN-gamma levels in sera, as compared with C57BL/6 mice. alpha-GalCer induced a clear-cut diminution of clinical and histological arthritides. |
| 2385 | 16304639 | An anti-IL-10 receptor antibody abrogated the protective effect of alpha-GalCer, suggesting a key role for IL-10 in the protection against CIA by activated iNKT cells. |
| 2386 | 16304639 | Confirming these data, disease protection conferred by alpha-GalCer correlated with the ability of LN CD4+ cells to secrete larger amounts of IL-10. |
| 2387 | 16306335 | No significant differences between genotypes (24 I/I subjects versus 10 I/III or III/III subjects) were observed for gamma-interferon, tumor necrosis factor-alpha, or interleukin (IL)-4. |
| 2388 | 16306335 | By contrast, the I/III + III/III group showed a significant threefold higher IL-10 release in memory T-cells for whole proinsulin and the immunodominant region. |
| 2389 | 16306335 | Given that IL-10 is a marker of regulatory function, our data are consistent with the hypothesis that higher insulin levels in the thymus promote the formation of regulatory T-cells, a proposed explanation for the protective effect of the class III alleles. |
| 2390 | 16329191 | Specific antiviral (self) CD8 T cells are mandatory for disease, but CD4 T cells are not. |
| 2391 | 16329191 | In this instance, diabetes can occur in the absence of infection if interferon gamma or B7.1 molecules are also expressed in the islets but not when IL-2, IL-4, IL-10, or IL-12 is similarly expressed. |
| 2392 | 16329191 | In contrast, both CD8 and CD4 antiviral (self) specific T cells are required when the self "viral" transgene is expressed concomitantly in beta cells and in the thymus. |
| 2393 | 16367949 | Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) we studied the expression levels of interleukin (IL)-2, IL-4, IL-10, IL-12, IL-15, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha during the course of LTB and SPTB in the lungs and spleens of B6D2F1Bom mice infected with the H37Rv strain of Mycobacterium tuberculosis (Mtb). |
| 2394 | 16367949 | The results show that, except for IL-4, cytokine expression levels were significantly higher during SPTB than LTB in both the lungs and spleens. |
| 2395 | 16367949 | During LTB, all the cytokines (except IL-2 in the lungs) had higher expression levels during the initial period of infection both in the lungs and spleens. |
| 2396 | 16367949 | The expression levels of IL-10, IL-12 and IFN-gamma increased significantly from 2 to 3 in the lungs. |
| 2397 | 16367949 | IL-10 and IL-15 increased significantly from phases 2 to 3, whereas that of TNF-alpha decreased significantly and progressively from phases 1 to 3 in the spleens. |
| 2398 | 16367949 | In the present study, there was a progressive and significant increase in the expression levels of IL-15, together with Th1 cytokines (IL-12 and IFN-gamma) during SPTB but a significant decrease during LTB. |
| 2399 | 16367949 | IL-15 is known to up-regulate the production of proinflammatory cytokines, IL-1beta, IL-8, IL-12, IL-17, IFN-gamma and TNF-alpha and has an inhibitory effect on activation-induced cell death. |
| 2400 | 16367949 | Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) we studied the expression levels of interleukin (IL)-2, IL-4, IL-10, IL-12, IL-15, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha during the course of LTB and SPTB in the lungs and spleens of B6D2F1Bom mice infected with the H37Rv strain of Mycobacterium tuberculosis (Mtb). |
| 2401 | 16367949 | The results show that, except for IL-4, cytokine expression levels were significantly higher during SPTB than LTB in both the lungs and spleens. |
| 2402 | 16367949 | During LTB, all the cytokines (except IL-2 in the lungs) had higher expression levels during the initial period of infection both in the lungs and spleens. |
| 2403 | 16367949 | The expression levels of IL-10, IL-12 and IFN-gamma increased significantly from 2 to 3 in the lungs. |
| 2404 | 16367949 | IL-10 and IL-15 increased significantly from phases 2 to 3, whereas that of TNF-alpha decreased significantly and progressively from phases 1 to 3 in the spleens. |
| 2405 | 16367949 | In the present study, there was a progressive and significant increase in the expression levels of IL-15, together with Th1 cytokines (IL-12 and IFN-gamma) during SPTB but a significant decrease during LTB. |
| 2406 | 16367949 | IL-15 is known to up-regulate the production of proinflammatory cytokines, IL-1beta, IL-8, IL-12, IL-17, IFN-gamma and TNF-alpha and has an inhibitory effect on activation-induced cell death. |
| 2407 | 16380491 | Using genetically deficient mice and cytokine-neutralizing monoclonal antibodies, we demonstrate here that the therapeutic effect does not involve T-helper type 2 cytokines (interleukin [IL]-4 and -10) but is tightly dependent on transforming growth factor (TGF)-beta. |
| 2408 | 16387690 | On activation, NF-kappaB regulates the expression of almost 400 different genes, which include enzymes (e.g., COX-2, 5-LOX, and iNOS), cytokines (such as TNF, IL-1, IL-6, IL-8, and chemokines), adhesion molecules, cell cycle regulatory molecules, viral proteins, and angiogenic factors. |
| 2409 | 16387690 | Several agents are known to suppress NF-kappaB activation, including Th2 cytokines (IL-4, IL-13, and IL-10), interferons, endocrine hormones (LH, HCG, MSH, and GH), phytochemicals, corticosteroids, and immunosuppressive agents. |
| 2410 | 16390542 | In vivo administration of siRNA admixed with the oil-based contrast agent lipiodol in the presence of antigen and adjuvant induced a deviation in recall response to reduced production of IFN-gamma and augmented IL-4 response using either KLH or ovalbumin. |
| 2411 | 16476010 | Elimination of CD4+ CD25+ regulatory T cells breaks down reovirus type 2-triggered and CpG ODN-induced prolonged mild autoimmune insulitis in DBA/1 mice. |
| 2412 | 16476010 | Compared with the control mice, newborn mice treated with monoclonal antibody (MoAb) against mouse CD25(+) CD4(+) T cells together with Reo-2 and CpG ODN greatly reduced the absolute number of splenic CD25(+) T cells and resulted in the development of severe insulitis, leading to an overt early diabetes. |
| 2413 | 16476010 | Moreover, the treatment of the MoAb increased production of interferon-gamma (IFN-gamma) and decreased that of interleukin-4 (IL-4) and transforming growth factor-beta1 (TGF-beta1) and developed high titre of autoantibodies against pancreatic islet cells. |
| 2414 | 16476010 | These evidences suggest that CD4(+) CD25(+) T cell may, at least in part, maintain tolerance to Reo-2-triggered and CpG ODN-induced prolonged mild Th1-dependent autoimmune insulitis, leading to the overt disease. |
| 2415 | 16492987 | In ELISPOT assay, IFN-gamma-secreting T cells, but not IL-4, against several insulin peptides were observed in 77.8% of patients with recent-onset T1D, 50.0% of patients with established T1D, and 0% of healthy control subjects. |
| 2416 | 16492987 | These data did not correlate with insulin autoantibodies or HLA-DRB1 of the patients. |
| 2417 | 16505600 | iNKT cells are a unique subset of CD1-restricted T lymphocytes that express T cell receptor (TCR) and some NK receptors. iNKT cells express an invariant TCRalpha chain composed of Valpha14-Jalpha18 segments in mice and Valpha24-Jalpha18 segments in humans associated with TCRbeta chains using a restricted set of Vbeta. iNKT cells recognize glycolipid antigens such as alpha-galactosylceramide (alpha-GC) presented by CD1d, non-pormorphic MHC class I-like molecule, and rapidly secrete large amounts of cytokines including IL-4 and IFN-gamma upon activation. |
| 2418 | 16533984 | Diabetic mice showed significantly higher levels of C-reactive protein, fibrinogen, fibronectin and von Willebrand factor than nondiabetic mice (P<0.05), and MRSA infection further elevated the plasma levels of these inflammatory and endothelial markers (P<0.05). |
| 2419 | 16533984 | Before infection, diabetic mice had significantly higher plasminogen activator inhibitor-1 (PAI-1) activity, lower antithrombin III (AT-III) and protein C activities (P<0.05), and MRSA infection significantly increased PAI-1 activity further and reduced the activity of AT-III and protein C (P<0.05). |
| 2420 | 16533984 | MRSA infection increased the production of three Th1 cytokines, interleukin 2 (IL-2), tumour necrosis factor alpha and gamma interferon, in diabetic mice (P<0.05); however, three Th2 cytokines, IL-4, IL-6, IL-10, were elevated at 2 and 4 days p.i., and then dropped gradually. |
| 2421 | 16628253 | In vivo, expansion of CD25(+)Foxp3(+) and insulin-specific Tregs producing IL-10, TGF-beta, and IL-4 was strongly enhanced. |
| 2422 | 16698671 | CBD treatment also resulted in the significant reduction of plasma levels of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha. |
| 2423 | 16698671 | Th1-associated cytokine production of in vitro activated T-cells and peritoneal macrophages was also significantly reduced in CBD-treated mice, whereas production of the Th2-associated cytokines, IL-4 and IL-10, was increased when compared to untreated control mice. |
| 2424 | 16700887 | This is perhaps more surprising, given that helminths often induce strong Th2-type immune responses characterized by release of specific cytokines, such as interleukin (IL)-4, IL-5 and IL-13. 4. |
| 2425 | 16704296 | Using the sensitive enzyme-linked immunospot (ELISPOT) technique to distinguish Th1-like from Th2-like lymphocytes, secretion of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was analyzed from PBMCs spontaneously and after in vitro stimulation with the diabetes-associated autoantigens, glutamic acid decarboxylase 65 (GAD65, protein and peptide, aa 247-279), recombinant tyrosine phosphatase (IA-2), and heat shock protein (HSP, aa 437-460). |
| 2426 | 16704296 | Secretion of IFN-gamma and the IFN-gamma/IL-4 ratio, induced by autoantigens, decreased in individuals developing T1D (p < 0.05), whereas nondiabetic individuals showed an increased IL-4 response (p < 0.05). |
| 2427 | 16704296 | Using the sensitive enzyme-linked immunospot (ELISPOT) technique to distinguish Th1-like from Th2-like lymphocytes, secretion of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was analyzed from PBMCs spontaneously and after in vitro stimulation with the diabetes-associated autoantigens, glutamic acid decarboxylase 65 (GAD65, protein and peptide, aa 247-279), recombinant tyrosine phosphatase (IA-2), and heat shock protein (HSP, aa 437-460). |
| 2428 | 16704296 | Secretion of IFN-gamma and the IFN-gamma/IL-4 ratio, induced by autoantigens, decreased in individuals developing T1D (p < 0.05), whereas nondiabetic individuals showed an increased IL-4 response (p < 0.05). |
| 2429 | 16707476 | As expected, adipokines (i.e., leptin, adiponectin, and resistin) were undetectable or found at very low levels in the blood of fatless mice. |
| 2430 | 16707476 | However, insulin, insulin-like growth factor-I, growth hormone, vascular endothelial growth factor, and proinflammatory Th2 cytokines, such as interleukin (IL)-1beta, IL-4, and IL-6, were elevated in A-ZIP/F-1 mice. |
| 2431 | 16707476 | Additionally, we examined multiple phosphorylated proteins (i.e., protein kinase B/Akt and ErbB2/HER-2 kinase) associated with cancer development. |
| 2432 | 16709804 | Anergic cells express transcripts that are associated with effector differentiation, e.g., the effector cytokines IL-4 and IFN-gamma. |
| 2433 | 16713180 | The mRNAs of IL-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine) were downregulated in the pancreas and spleen of diabetic pregnant rats. |
| 2434 | 16713180 | Feeding an n-3 PUFA diet to rats with DP upregulated IL-10 mRNA in the pancreas and IL-4 and IL-10 mRNA in the spleen. |
| 2435 | 16713180 | In MAC offspring, high expression of IL-2 and IFN-gamma mRNA, but not of Th2 cytokines, was observed. |
| 2436 | 16713180 | The n-3 PUFA diet diminished Th1 mRNA quantities and increased the levels of IL-4, but not of IL-10, mRNA in MAC offspring. |
| 2437 | 16713180 | The mRNAs of IL-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine) were downregulated in the pancreas and spleen of diabetic pregnant rats. |
| 2438 | 16713180 | Feeding an n-3 PUFA diet to rats with DP upregulated IL-10 mRNA in the pancreas and IL-4 and IL-10 mRNA in the spleen. |
| 2439 | 16713180 | In MAC offspring, high expression of IL-2 and IFN-gamma mRNA, but not of Th2 cytokines, was observed. |
| 2440 | 16713180 | The n-3 PUFA diet diminished Th1 mRNA quantities and increased the levels of IL-4, but not of IL-10, mRNA in MAC offspring. |
| 2441 | 16713180 | The mRNAs of IL-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine) were downregulated in the pancreas and spleen of diabetic pregnant rats. |
| 2442 | 16713180 | Feeding an n-3 PUFA diet to rats with DP upregulated IL-10 mRNA in the pancreas and IL-4 and IL-10 mRNA in the spleen. |
| 2443 | 16713180 | In MAC offspring, high expression of IL-2 and IFN-gamma mRNA, but not of Th2 cytokines, was observed. |
| 2444 | 16713180 | The n-3 PUFA diet diminished Th1 mRNA quantities and increased the levels of IL-4, but not of IL-10, mRNA in MAC offspring. |
| 2445 | 16713232 | Caloric restriction inhibits up-regulation of inflammatory cytokines and TNF-alpha, and activates IL-10 and haptoglobin in the plasma of streptozotocin-induced diabetic rats. |
| 2446 | 16713232 | The inflammatory cytokines [interleukin (IL)-1beta, IL-4 and IL-6] and tumor necrosis factor alpha up-regulated in diabetes were found to be significantly depressed by CR, whereas the antiinflammatory mediators, haptoglobin and IL-10 levels, were increased. |
| 2447 | 16717396 | Peripheral blood mononuclear cells of all subjects were examined by flow cytometry for intracellular cytokines (IFN-gamma for Th1; IL-4 for Th2) and expression of the chemokine receptors CXCR3 (Th1-associated) and CCR4 (Th2-associated). |
| 2448 | 16717396 | Plasma concentrations of interferon-inducible protein (IP)-10, a CXCR3 ligand, and thymus and activation-regulated chemokine (TARC), a CCR4 ligand, were measured by enzyme-linked immunosorbent assays. |
| 2449 | 16717396 | Considering only patients with type 1 diabetes alone, duration of diabetes correlated positively with IFN-gamma-producing T lymphocytes (r = 0.773, P = 0.0242) and the ratio of CXCR3 to CCR4 receptor expression (r = 0.947, P = 0.0004). |
| 2450 | 16764688 | Prior epicutaneous immunization results in reduced production of antigen-specific interferon-gamma and immunoglobulin G2a (IgG2a) and enhanced interleukin-4, IgG1 and IgE responses to immunization with CFA. |
| 2451 | 16764688 | Moreover, epicutaneous immunization converts an established Th1 response to a Th2 response, as demonstrated by the specific reduction of interferon-gamma and IgG2a and the enhancement of interleukin-4 and IgE. |
| 2452 | 16764688 | Prior epicutaneous immunization results in reduced production of antigen-specific interferon-gamma and immunoglobulin G2a (IgG2a) and enhanced interleukin-4, IgG1 and IgE responses to immunization with CFA. |
| 2453 | 16764688 | Moreover, epicutaneous immunization converts an established Th1 response to a Th2 response, as demonstrated by the specific reduction of interferon-gamma and IgG2a and the enhancement of interleukin-4 and IgE. |
| 2454 | 16879245 | The expression of interferon (IFN)-gamma, interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-beta in PBMC was studied with real-time polymerase chain reaction (PCR) in a subgroup of 38 children. |
| 2455 | 16879245 | Rotavirus-stimulated lymphocytes from autoantibody-positive children produced more IL-4 and phytohaemagglutinin (PHA)-stimulated lymphocytes more IL-4 and IFN-gamma than lymphocytes from control children. |
| 2456 | 16879245 | PHA-stimulated lymphocytes from children with diabetes also produced more IL-4 and purified protein derivative (PPD)-stimulated lymphocytes less TGF-beta than lymphocytes from autoantibody-negative control children. |
| 2457 | 16879245 | The expression of interferon (IFN)-gamma, interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-beta in PBMC was studied with real-time polymerase chain reaction (PCR) in a subgroup of 38 children. |
| 2458 | 16879245 | Rotavirus-stimulated lymphocytes from autoantibody-positive children produced more IL-4 and phytohaemagglutinin (PHA)-stimulated lymphocytes more IL-4 and IFN-gamma than lymphocytes from control children. |
| 2459 | 16879245 | PHA-stimulated lymphocytes from children with diabetes also produced more IL-4 and purified protein derivative (PPD)-stimulated lymphocytes less TGF-beta than lymphocytes from autoantibody-negative control children. |
| 2460 | 16879245 | The expression of interferon (IFN)-gamma, interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-beta in PBMC was studied with real-time polymerase chain reaction (PCR) in a subgroup of 38 children. |
| 2461 | 16879245 | Rotavirus-stimulated lymphocytes from autoantibody-positive children produced more IL-4 and phytohaemagglutinin (PHA)-stimulated lymphocytes more IL-4 and IFN-gamma than lymphocytes from control children. |
| 2462 | 16879245 | PHA-stimulated lymphocytes from children with diabetes also produced more IL-4 and purified protein derivative (PPD)-stimulated lymphocytes less TGF-beta than lymphocytes from autoantibody-negative control children. |
| 2463 | 16970111 | Tosilate of suplatast is a selective IL-4 and IL-5 inhibitor. |
| 2464 | 16972262 | BB rats were therefore checked at day 21 up to day 90 of life for blood glucose, insulin levels, degree of islet infiltration, expression of proinflammatory and protective cytokines and antibodies including CD4, CD8, CD25, LFA-1, and ICAM-1. |
| 2465 | 16972262 | We found that islets of non-diabetic BB rats became positive to both IL-1beta and IL-4 very early on, confirming a local but intense production of both cytokines within the islets during the initial non-diabetic period. |
| 2466 | 16972262 | In addition, we observed that the production of these interleukins together with the expression levels of CD4 and CD25 are events predictive for type 1 diabetes onset in non-diabetic BB rats, as for non-obese diabetic (NOD) mice. |
| 2467 | 16972262 | In particular, the production of IL-1beta and IL-4 during the non-diabetic period together with the lack of enhancement of CD4 and CD25, indicating selective recruitment of activated T cells, may explain the failure of anti-diabetic treatments in this animal model of type 1 diabetes. |
| 2468 | 16972262 | BB rats were therefore checked at day 21 up to day 90 of life for blood glucose, insulin levels, degree of islet infiltration, expression of proinflammatory and protective cytokines and antibodies including CD4, CD8, CD25, LFA-1, and ICAM-1. |
| 2469 | 16972262 | We found that islets of non-diabetic BB rats became positive to both IL-1beta and IL-4 very early on, confirming a local but intense production of both cytokines within the islets during the initial non-diabetic period. |
| 2470 | 16972262 | In addition, we observed that the production of these interleukins together with the expression levels of CD4 and CD25 are events predictive for type 1 diabetes onset in non-diabetic BB rats, as for non-obese diabetic (NOD) mice. |
| 2471 | 16972262 | In particular, the production of IL-1beta and IL-4 during the non-diabetic period together with the lack of enhancement of CD4 and CD25, indicating selective recruitment of activated T cells, may explain the failure of anti-diabetic treatments in this animal model of type 1 diabetes. |
| 2472 | 17008395 | This result correlated with a corresponding change in cytokine secretion, with the interferon-gamma to IL-4 ratio being decreased by 33%. |
| 2473 | 17032237 | Indeed, on in vitro ovalbumin stimulation, spleen T cells from naive HFD-fed transgenic mice showed proliferation similar to that of cells from standard diet (SD)-fed mice, but exhibited a strong inflammatory profile as shown by the markedly increased IFN-gamma/IL-4 ratio. |
| 2474 | 17100636 | NKT cells are a subset of regulatory lymphocytes characterized by co-expression of the NK cell receptor-CD161 and an invariant TCR-alpha chain (Valpha14-Jalpha28). |
| 2475 | 17100636 | Activation of NKT lymphocytes leads to rapid amplification of either IFNgamma or IL4, endowing these cells with the capability to mediate both pro-inflammatory and anti-inflammatory immune responses. |
| 2476 | 17100636 | Administration of CD1d ligand has a protective role in collagen-induced arthritis in mice. |
| 2477 | 17100636 | NKT lymphocytes are activated by interaction of their TCR with glycolipids presented by CD1d, a nonpolymorphic, MHC class I-like molecule expressed by antigen presenting cells, and also by hepatocytes. |
| 2478 | 17100636 | On the other hand, glucosylceramide-synthase deficiency was shown to lead to defective ligand presentation by CD1d, with secondary inhibition of NKT cell activation. |
| 2479 | 17100762 | Using the enzyme-linked immunospot (ELISPOT) technique, interferon (IFN)-gamma and interleukin (IL)-4 were analysed from fresh PBMC spontaneously and after in vitro stimulation with antigens associated with one or more of these diseases (insulin, gluten, birch and cat extract, beta-lactoglobulin, ovalbumin and phytohaemagglutinin) in order to divide T helper (Th)1- from Th2-like lymphocytes. |
| 2480 | 17100762 | A low IFN-gamma response to insulin was found in type 1 diabetic children, whereas allergic children responded to insulin by increased IL-4 secretion. |
| 2481 | 17100762 | Using the enzyme-linked immunospot (ELISPOT) technique, interferon (IFN)-gamma and interleukin (IL)-4 were analysed from fresh PBMC spontaneously and after in vitro stimulation with antigens associated with one or more of these diseases (insulin, gluten, birch and cat extract, beta-lactoglobulin, ovalbumin and phytohaemagglutinin) in order to divide T helper (Th)1- from Th2-like lymphocytes. |
| 2482 | 17100762 | A low IFN-gamma response to insulin was found in type 1 diabetic children, whereas allergic children responded to insulin by increased IL-4 secretion. |
| 2483 | 17101254 | Accordingly, cytopiloyne also suppressed IFN-gamma expression and promoted IL-4 expression in mouse splenocytes ex vivo. |
| 2484 | 17130491 | Natural CD4(+)CD25(high) regulatory T-cells are derived from thymus, and accordingly human insulin-specific regulatory T-cells should exist. |
| 2485 | 17130491 | The mRNA expression of regulatory T-cell markers (transforming growth factor-beta, Foxp3, cytotoxic T-lymphocyte antigen-4 [CTLA-4], and inducible co-stimulator [ICOS]) or cytokines (gamma-interferon [IFN-gamma], interleukin [IL]-5, IL-4) was measured by quantitative RT-PCR. |
| 2486 | 17130491 | The secretion of IFN-gamma, IL-2, IL-4, IL-5, and IL-10 was also studied. |
| 2487 | 17130491 | The expression of Foxp3, CTLA-4, and ICOS mRNAs in PBMCs stimulated with bovine or human insulin was higher in patients on insulin treatment than in patients studied before starting insulin treatment. |
| 2488 | 17130491 | The insulin-induced Foxp3 protein expression in CD4(+)CD25(high) cells was detectable in flow cytometry. |
| 2489 | 17130491 | Insulin stimulation in vitro induced increased expression of regulatory T-cell markers, Foxp3, CTLA-4, and ICOS only in patients treated with insulin, suggesting that treatment with human insulin activates insulin-specific regulatory T-cells in children with newly diagnosed type 1 diabetes. |
| 2490 | 17130491 | Natural CD4(+)CD25(high) regulatory T-cells are derived from thymus, and accordingly human insulin-specific regulatory T-cells should exist. |
| 2491 | 17130491 | The mRNA expression of regulatory T-cell markers (transforming growth factor-beta, Foxp3, cytotoxic T-lymphocyte antigen-4 [CTLA-4], and inducible co-stimulator [ICOS]) or cytokines (gamma-interferon [IFN-gamma], interleukin [IL]-5, IL-4) was measured by quantitative RT-PCR. |
| 2492 | 17130491 | The secretion of IFN-gamma, IL-2, IL-4, IL-5, and IL-10 was also studied. |
| 2493 | 17130491 | The expression of Foxp3, CTLA-4, and ICOS mRNAs in PBMCs stimulated with bovine or human insulin was higher in patients on insulin treatment than in patients studied before starting insulin treatment. |
| 2494 | 17130491 | The insulin-induced Foxp3 protein expression in CD4(+)CD25(high) cells was detectable in flow cytometry. |
| 2495 | 17130491 | Insulin stimulation in vitro induced increased expression of regulatory T-cell markers, Foxp3, CTLA-4, and ICOS only in patients treated with insulin, suggesting that treatment with human insulin activates insulin-specific regulatory T-cells in children with newly diagnosed type 1 diabetes. |
| 2496 | 17130537 | To address DC dysregulation we examined kinetic global gene expression in NOD and B6 GM-CSF/IL-4-induced bone marrow-derived DC following lipopolysaccharide (LPS)-stimulation. |
| 2497 | 17130537 | Mechanistically, heightened IFN-alpha/beta responses were not due to increased production of this cytokine, IFN-gamma priming or increased Syk kinase activity. |
| 2498 | 17130537 | We found, however, heightened responses to IFN-alpha/beta in NOD versus B6 as demonstrated by increased type 1 IFN target gene expression, for example, IRF-7, in NOD DC and macrophages. |
| 2499 | 17151140 | We tested CD4, CD8, and CD161 expression and IL-4 and IFN-gamma production on TCR stimulation. |
| 2500 | 17162357 | Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-beta) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. |
| 2501 | 17162357 | Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. |
| 2502 | 17162357 | Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-beta) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. |
| 2503 | 17162357 | Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. |
| 2504 | 17164429 | Distinct regulation of autoreactive CD4 T cell expansion by interleukin-4 under conditions of lymphopenia. |
| 2505 | 17164429 | Here, we show that IL-4 only enhances the expansion of autoreactive CD4 T cells during lymphopenia and that neither the presence of islet IL-4 nor IL-4 deficiency affects T cell expansion significantly under conditions of immunosufficiency. |
| 2506 | 17164429 | The ability of IL-4 to promote autoreactive CD4 T cell expansion is therefore sensitive to the degree of host immunodeficiency. |
| 2507 | 17164429 | Paradoxically, IL-4 receptor-deficient, autoreactive CD4 T cells proliferate more extensively than wild-type T cells in immunodeficient hosts, suggesting that the growth-promoting effect of islet IL-4 acts indirectly. |
| 2508 | 17164429 | Distinct regulation of autoreactive CD4 T cell expansion by interleukin-4 under conditions of lymphopenia. |
| 2509 | 17164429 | Here, we show that IL-4 only enhances the expansion of autoreactive CD4 T cells during lymphopenia and that neither the presence of islet IL-4 nor IL-4 deficiency affects T cell expansion significantly under conditions of immunosufficiency. |
| 2510 | 17164429 | The ability of IL-4 to promote autoreactive CD4 T cell expansion is therefore sensitive to the degree of host immunodeficiency. |
| 2511 | 17164429 | Paradoxically, IL-4 receptor-deficient, autoreactive CD4 T cells proliferate more extensively than wild-type T cells in immunodeficient hosts, suggesting that the growth-promoting effect of islet IL-4 acts indirectly. |
| 2512 | 17164429 | Distinct regulation of autoreactive CD4 T cell expansion by interleukin-4 under conditions of lymphopenia. |
| 2513 | 17164429 | Here, we show that IL-4 only enhances the expansion of autoreactive CD4 T cells during lymphopenia and that neither the presence of islet IL-4 nor IL-4 deficiency affects T cell expansion significantly under conditions of immunosufficiency. |
| 2514 | 17164429 | The ability of IL-4 to promote autoreactive CD4 T cell expansion is therefore sensitive to the degree of host immunodeficiency. |
| 2515 | 17164429 | Paradoxically, IL-4 receptor-deficient, autoreactive CD4 T cells proliferate more extensively than wild-type T cells in immunodeficient hosts, suggesting that the growth-promoting effect of islet IL-4 acts indirectly. |
| 2516 | 17164429 | Distinct regulation of autoreactive CD4 T cell expansion by interleukin-4 under conditions of lymphopenia. |
| 2517 | 17164429 | Here, we show that IL-4 only enhances the expansion of autoreactive CD4 T cells during lymphopenia and that neither the presence of islet IL-4 nor IL-4 deficiency affects T cell expansion significantly under conditions of immunosufficiency. |
| 2518 | 17164429 | The ability of IL-4 to promote autoreactive CD4 T cell expansion is therefore sensitive to the degree of host immunodeficiency. |
| 2519 | 17164429 | Paradoxically, IL-4 receptor-deficient, autoreactive CD4 T cells proliferate more extensively than wild-type T cells in immunodeficient hosts, suggesting that the growth-promoting effect of islet IL-4 acts indirectly. |
| 2520 | 17177137 | Histological studies evaluated insulitis development and Western blot analysis was employed to evaluate the expression levels of Th1 cytokines (TNF-alpha and IFN-gamma) and Th2 cytokines (IL-10 and IL-4). |
| 2521 | 17192467 | Induction of indoleamine 2,3-dioxygenase by interferon-gamma in human islets. |
| 2522 | 17192467 | Microarray and quantitative PCR analyses of isolated human islets incubated with interferon (IFN)-gamma for 24 h revealed increased expression of IDO mRNA (>139-fold) and Trp-tRNA synthase (WARS) (>17-fold) along with 975 other transcripts more than threefold, notably the downstream effectors janus kinase (JAK)2, signal transducer and activator of transcription (STAT)1, IFN-gamma regulatory factor-1, and several chemokines (CXCL9/MIG, CXCL10/IP10, CXCL11/1-TAC, CCL2, and CCL5/RANTES) and their receptors. |
| 2523 | 17192467 | IDO protein expression was upregulated in IFN-gamma-treated islets and accompanied by increased intracellular IDO enzyme activity and the release of KYN into the media. |
| 2524 | 17192467 | The response to IFN-gamma was countered by interleukin-4 and 1alpha-methyl Trp. |
| 2525 | 17192467 | Immunohistochemical localization showed IDO to be induced in cells of both endocrine, including pancreatic duodenal homeobox 1-positive beta-cells, and nonendocrine origin. |
| 2526 | 17202329 | We show that KRV infection strongly stimulates BBDR splenocytes to produce the proinflammatory cytokines IL-6 and IL-12p40 but not TNF-alpha. |
| 2527 | 17202329 | KRV infection induces high levels of IL-12p40 by splenic B cells and Flt-3-ligand-induced bone marrow-derived dendritic cells (DCs) but only low levels of IL-12p40 production by thioglycolate-elicited peritoneal macrophages or GM-CSF plus IL-4-induced bone marrow-derived DCs. |
| 2528 | 17213232 | We investigated the relationship of nine common single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, IL-4 and transforming growth factor (TGF)-beta1 with the atherosclerotic severity in 10 different arteries based on 1503 consecutive autopsies of elderly Japanese subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study. |
| 2529 | 17213232 | The -511T of IL-1beta and the +29T of TGF-beta1 were significant risk factors for atherogenesis in the subclavian and intracranial arteries (OR: 1.35 and 1.48, respectively). |
| 2530 | 17213232 | Functional SNPs in TNF-alpha, IL-1beta and TGF-beta1 genes play a role in atherogenesis, although their influences are less pronounced than those of conventional risk factors and appear to be limited to specific arteries in the Japanese elderly. |
| 2531 | 17237379 | We recently showed that neither iNKT cell protection against diabetes nor iNKT cell inhibition of T cell differentiation in vitro requires cytokines such as IL-4, IL-10, IL-13, and TGF-beta. |
| 2532 | 17302896 | We therefore examined the recently activated circulating T cell population [CD3+, human leucocyte antigen D-related (HLA-DR+)] using cytokine production and 10 additional subset markers [CD69, CD25, CD122, CD30, CD44v6, CD57, CD71, CCR3 (CD193), CCR5 (CD195) or CXCR3 (CD183)], comparing newly diagnosed adult (ND) (age 18-40 years) patients (n=19) to patients with diabetes for >10 years [long-standing (LS), n=19] and HLA-matched controls (C, n=16). |
| 2533 | 17302896 | No differences in basal or stimulated production of interleukin (IL)-4, IL-10, IL-13 or interferon (IFN)-gamma by CD3+ DR+ enriched cells were observed between the different groups of subjects. |
| 2534 | 17302896 | However, among the CD3+ DR+ population, significant expansions appeared to be present in the very small CD30+, CD69+ and CD122+ subpopulations. |
| 2535 | 17302896 | A confirmatory study was then performed using new subjects (ND=26, LS=15), three-colour flow cytometry, unseparated cells and three additional subset markers (CD38, CD134, CD4/CD25). |
| 2536 | 17317763 | To define the parameters influencing the efficacy of antigen-specific immunotherapy once diabetes is established, plasmid DNA (pDNA) vaccination was used to suppress autoimmune-mediated destruction of syngeneic islet grafts in diabetic NOD recipients. pDNAs encoding a glutamic acid decarboxylase 65 (GAD65)-Ig molecule (pGAD65), interleukin (IL)-4 (pIL4), and IL-10 (pIL10) significantly delayed the onset of recurrent diabetes compared with pGAD65+pIL10-vaccinated recipients. |
| 2537 | 17317763 | Despite differences in efficacy, a similar frequency of GAD65-specific CD4(+) T-cells secreting IL-4, IL-10, or interferon-gamma were detected in mice treated with pGAD65+pIL4+pIL10 and pGAD65+pIL10. |
| 2538 | 17317763 | However, the frequency of FoxP3-expressing CD4(+)CD25(+)CD62L(hi) T-cells was increased in the renal and pancreatic lymph nodes of diabetic recipients vaccinated with pGAD65+pIL4+pIL10. |
| 2539 | 17317763 | These immunoregulatory CD4(+)CD25(+) T-cells (CD4(+)CD25(+) Treg) exhibited enhanced in vivo and in vitro suppressor activity that partially was transforming growth factor-beta dependent. |
| 2540 | 17317763 | Furthermore, duration of islet graft protection in pGAD65+pIL4+pIL10-vaccinated diabetic recipients correlated with the persistence of CD4(+)CD25(+) Treg. |
| 2541 | 17317763 | These data demonstrate that the frequency and maintenance of FoxP3-expressing CD4(+)CD25(+) Treg influence antigen-induced suppression of ongoing beta-cell autoimmunity in diabetic recipients. |
| 2542 | 17317763 | To define the parameters influencing the efficacy of antigen-specific immunotherapy once diabetes is established, plasmid DNA (pDNA) vaccination was used to suppress autoimmune-mediated destruction of syngeneic islet grafts in diabetic NOD recipients. pDNAs encoding a glutamic acid decarboxylase 65 (GAD65)-Ig molecule (pGAD65), interleukin (IL)-4 (pIL4), and IL-10 (pIL10) significantly delayed the onset of recurrent diabetes compared with pGAD65+pIL10-vaccinated recipients. |
| 2543 | 17317763 | Despite differences in efficacy, a similar frequency of GAD65-specific CD4(+) T-cells secreting IL-4, IL-10, or interferon-gamma were detected in mice treated with pGAD65+pIL4+pIL10 and pGAD65+pIL10. |
| 2544 | 17317763 | However, the frequency of FoxP3-expressing CD4(+)CD25(+)CD62L(hi) T-cells was increased in the renal and pancreatic lymph nodes of diabetic recipients vaccinated with pGAD65+pIL4+pIL10. |
| 2545 | 17317763 | These immunoregulatory CD4(+)CD25(+) T-cells (CD4(+)CD25(+) Treg) exhibited enhanced in vivo and in vitro suppressor activity that partially was transforming growth factor-beta dependent. |
| 2546 | 17317763 | Furthermore, duration of islet graft protection in pGAD65+pIL4+pIL10-vaccinated diabetic recipients correlated with the persistence of CD4(+)CD25(+) Treg. |
| 2547 | 17317763 | These data demonstrate that the frequency and maintenance of FoxP3-expressing CD4(+)CD25(+) Treg influence antigen-induced suppression of ongoing beta-cell autoimmunity in diabetic recipients. |
| 2548 | 17319946 | Interleukin-4 inhibition of interleukin-1-induced expression of matrix metalloproteinase-3 (MMP-3) is independent of lipoxygenase and PPARgamma activation in human gingival fibroblasts. |
| 2549 | 17327452 | Here, we show that antibody neutralization of CCL4 abrogates the ability of T-cells from IL-4-treated NOD mice to transfer protection against type 1 diabetes. |
| 2550 | 17339462 | Furthermore, we demonstrate that one of the IL-4 regulated genes, NDFIP2, promotes IFN-gamma production by the polarized human Th1 lymphocytes. |
| 2551 | 17374136 | The CXCR4/CXCL12 (SDF-1) signalling pathway protects non-obese diabetic mouse from autoimmune diabetes. |
| 2552 | 17374136 | The chemokine stromal cell-derived factor-1 CXCL-12 (SDF-1) and its ligand the CXCR4 chemokine receptor are important regulatory elements. |
| 2553 | 17374136 | CXCR4 is expressed on the surface of CD4(+) T cells, dendritic cells and B lymphocytes. |
| 2554 | 17374136 | This effect was associated with an increase of interferon (IFN)-gamma mRNA and a reduction of interleukin (IL)-4 mRNA levels both in PLNs and isolated islets. |
| 2555 | 17374136 | AMD3100 also reduced IL-4 and IL-10 production of plate-bound anti-CD3 and anti-CD28-stimulated splenocytes. |
| 2556 | 17374136 | Immunofluorescence studies indicated that AMD3100 reduced the number of CXCR4(+) and SDF-1 positive cells in the inflamed islets. |
| 2557 | 17374136 | We can conclude that the CXCL-12/CXCR4 pathway has protective effects against autoimmune diabetes. |
| 2558 | 17374136 | The CXCR4/CXCL12 (SDF-1) signalling pathway protects non-obese diabetic mouse from autoimmune diabetes. |
| 2559 | 17374136 | The chemokine stromal cell-derived factor-1 CXCL-12 (SDF-1) and its ligand the CXCR4 chemokine receptor are important regulatory elements. |
| 2560 | 17374136 | CXCR4 is expressed on the surface of CD4(+) T cells, dendritic cells and B lymphocytes. |
| 2561 | 17374136 | This effect was associated with an increase of interferon (IFN)-gamma mRNA and a reduction of interleukin (IL)-4 mRNA levels both in PLNs and isolated islets. |
| 2562 | 17374136 | AMD3100 also reduced IL-4 and IL-10 production of plate-bound anti-CD3 and anti-CD28-stimulated splenocytes. |
| 2563 | 17374136 | Immunofluorescence studies indicated that AMD3100 reduced the number of CXCR4(+) and SDF-1 positive cells in the inflamed islets. |
| 2564 | 17374136 | We can conclude that the CXCL-12/CXCR4 pathway has protective effects against autoimmune diabetes. |
| 2565 | 17403060 | Cells were pretreated in vitro with IL-4, incubated with IL-1beta and interferon (IFN)-gamma and DNA fragmentation and nitrite production analysed by flow cytometry and Griess assay, respectively. |
| 2566 | 17403060 | Expression of type I (IL-4R alpha and common gamma-chain) and type II (IL-4R alpha, IL-13R alpha-1) IL-4R mRNA transcripts, together with cell surface expression of IL-4R, was demonstrated. |
| 2567 | 17403060 | Pre-incubation with IL-4 reduced significantly cell death induced by IL-1beta alone or by a combination of IL-1beta and IFN-gamma, although this was not accompanied by a reduced production of nitrite. |
| 2568 | 17403060 | Cells were pretreated in vitro with IL-4, incubated with IL-1beta and interferon (IFN)-gamma and DNA fragmentation and nitrite production analysed by flow cytometry and Griess assay, respectively. |
| 2569 | 17403060 | Expression of type I (IL-4R alpha and common gamma-chain) and type II (IL-4R alpha, IL-13R alpha-1) IL-4R mRNA transcripts, together with cell surface expression of IL-4R, was demonstrated. |
| 2570 | 17403060 | Pre-incubation with IL-4 reduced significantly cell death induced by IL-1beta alone or by a combination of IL-1beta and IFN-gamma, although this was not accompanied by a reduced production of nitrite. |
| 2571 | 17440992 | The intake of SEC caused significantly dose-dependent increase in insulin and decrease in blood glucose, urinary albumin and type IV collagen (P < 0.05). |
| 2572 | 17440992 | SEC treatments dose-dependently decreased IL-6 and TNF-alpha levels, increased IL-4 and IL-10 levels, as well as upregulated IL-10 mRNA expression (P < 0.05). |
| 2573 | 17440992 | SMC treatments significantly suppressed renal IL-6 and TNF-alpha levels (P < 0.05), but did not affect IL-4 and IL-10 levels (P < 0.05). |
| 2574 | 17440992 | The intake of SEC caused significantly dose-dependent increase in insulin and decrease in blood glucose, urinary albumin and type IV collagen (P < 0.05). |
| 2575 | 17440992 | SEC treatments dose-dependently decreased IL-6 and TNF-alpha levels, increased IL-4 and IL-10 levels, as well as upregulated IL-10 mRNA expression (P < 0.05). |
| 2576 | 17440992 | SMC treatments significantly suppressed renal IL-6 and TNF-alpha levels (P < 0.05), but did not affect IL-4 and IL-10 levels (P < 0.05). |
| 2577 | 17490448 | Increased expression of immunosuppressive cytokines, such as interleukin-4 and interleukin-10 (IL-4 and IL-10), was observed in the pancreas of CTB-Pins-treated NOD mice. |
| 2578 | 17491692 | The studies were aimed at improving the effectiveness of Th2 cells to secrete the principal cytokines, IL-4 and IL-10, in order to mediate protection from diabetes in NOD mice. |
| 2579 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 2580 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 2581 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 2582 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 2583 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 2584 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 2585 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 2586 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 2587 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 2588 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 2589 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 2590 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 2591 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 2592 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 2593 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 2594 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 2595 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 2596 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 2597 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 2598 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 2599 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 2600 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 2601 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 2602 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 2603 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 2604 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 2605 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 2606 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 2607 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 2608 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 2609 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 2610 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 2611 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 2612 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 2613 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 2614 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 2615 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 2616 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 2617 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 2618 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 2619 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 2620 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 2621 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 2622 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 2623 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 2624 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 2625 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 2626 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 2627 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 2628 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 2629 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 2630 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 2631 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 2632 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 2633 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 2634 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 2635 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 2636 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 2637 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 2638 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 2639 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 2640 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 2641 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 2642 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 2643 | 17611256 | It results in insulin deficiency as a consequence of autoimmune destruction of islet beta-cells in the pancreas and is believed to be mediated by Th1 cytokines (IFNgamma, TNFalpha, and IL-2). |
| 2644 | 17611256 | A number of genes have been associated with type 1 diabetes in humans, including the human leukocyte antigen region, the insulin variable number tandem repeat, PTPN22, CTLA4, IL-4, and IL-13. |
| 2645 | 17611256 | In this study, 483 cases of canine diabetes and 869 controls of known breed were analyzed for association with IFNgamma, IGF2, IL-10, IL-12beta, IL-6, insulin, PTPN22, RANTES, IL-4, IL-1alpha and TNFalpha. |
| 2646 | 17611256 | Some associations were with increased susceptibility to the disease (IFNgamma, IL-10, IL-12beta, IL-6, insulin, PTPN22, IL-4, and TNFalpha), whereas others were protective (IL-4, PTPN22, IL-6, insulin, IGF2, TNFalpha). |
| 2647 | 17611256 | It results in insulin deficiency as a consequence of autoimmune destruction of islet beta-cells in the pancreas and is believed to be mediated by Th1 cytokines (IFNgamma, TNFalpha, and IL-2). |
| 2648 | 17611256 | A number of genes have been associated with type 1 diabetes in humans, including the human leukocyte antigen region, the insulin variable number tandem repeat, PTPN22, CTLA4, IL-4, and IL-13. |
| 2649 | 17611256 | In this study, 483 cases of canine diabetes and 869 controls of known breed were analyzed for association with IFNgamma, IGF2, IL-10, IL-12beta, IL-6, insulin, PTPN22, RANTES, IL-4, IL-1alpha and TNFalpha. |
| 2650 | 17611256 | Some associations were with increased susceptibility to the disease (IFNgamma, IL-10, IL-12beta, IL-6, insulin, PTPN22, IL-4, and TNFalpha), whereas others were protective (IL-4, PTPN22, IL-6, insulin, IGF2, TNFalpha). |
| 2651 | 17611256 | It results in insulin deficiency as a consequence of autoimmune destruction of islet beta-cells in the pancreas and is believed to be mediated by Th1 cytokines (IFNgamma, TNFalpha, and IL-2). |
| 2652 | 17611256 | A number of genes have been associated with type 1 diabetes in humans, including the human leukocyte antigen region, the insulin variable number tandem repeat, PTPN22, CTLA4, IL-4, and IL-13. |
| 2653 | 17611256 | In this study, 483 cases of canine diabetes and 869 controls of known breed were analyzed for association with IFNgamma, IGF2, IL-10, IL-12beta, IL-6, insulin, PTPN22, RANTES, IL-4, IL-1alpha and TNFalpha. |
| 2654 | 17611256 | Some associations were with increased susceptibility to the disease (IFNgamma, IL-10, IL-12beta, IL-6, insulin, PTPN22, IL-4, and TNFalpha), whereas others were protective (IL-4, PTPN22, IL-6, insulin, IGF2, TNFalpha). |
| 2655 | 17708341 | The expression of IL-1beta, TNF-alpha, IFN-gamma, IL-6, IL-10, and IL-4 genes was determined by real-time PCR in freshly isolated islets, in 24-h cultured islets and in islet grafts on days 1, 3, and 7 after transplantation. |
| 2656 | 17708341 | IL-6 and IL-10 were not detected in freshly isolated islets, but their expression was clearly enhanced in 24-h cultured islets and islet grafts. |
| 2657 | 17708341 | IFN-gamma mRNA was barely detected in a few grafts, and IL-4 mRNA was never detected. |
| 2658 | 17708341 | The expression of IL-1beta, TNF-alpha, IFN-gamma, IL-6, IL-10, and IL-4 genes was determined by real-time PCR in freshly isolated islets, in 24-h cultured islets and in islet grafts on days 1, 3, and 7 after transplantation. |
| 2659 | 17708341 | IL-6 and IL-10 were not detected in freshly isolated islets, but their expression was clearly enhanced in 24-h cultured islets and islet grafts. |
| 2660 | 17708341 | IFN-gamma mRNA was barely detected in a few grafts, and IL-4 mRNA was never detected. |
| 2661 | 17709885 | Type 1 diabetes (T1D) results from autoimmune destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans by autoreactive T helper 1 (Th1) cells characterized by their cytokine secretory products, interleukin-2 (IL-2) and interferon gamma (IFNgamma). |
| 2662 | 17709885 | Th1-type cytokines (IL-2 and IFNgamma) correlate with T1D, whereas Th2 (IL-4 and IL-10), Th3 (transforming growth factor beta [TGFbeta]), and T regulatory cell-type cytokines (IL-10 and TGFbeta) correlate with protection from T1D. |
| 2663 | 17709885 | Paradoxically, however, administrations of Th1-type cytokines (IL-2 and IFNgamma) and immunotherapies that induce Th1-type cytokine responses actually prevent T1D, at least in animal models. |
| 2664 | 17927013 | Insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha (TNF-alpha), interleukins-6 (IL-6), macrophage migration inhibitory factor (MIF) and other pro-inflammatory cytokines and reactive oxygen species (ROS), enhances the synthesis of endothelial nitric oxide (eNO), and anti-inflammatory cytokines interleukins-4 (IL-4) and interleukin-10 (IL-10). |
| 2665 | 17927013 | In subjects who are critically ill, monocyte HLA-DR expression was significantly decreased with a concomitant increase in plasma IL-10 and IL-4 concentrations. |
| 2666 | 17927013 | Large increases in the plasma concentrations of TNF-alpha, IL-6, sustained increase in the expression of leukocyte CD11b/CD18, and ROS generation following surgery and infections were found to be associated with increased mortality. |
| 2667 | 17927013 | Insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha (TNF-alpha), interleukins-6 (IL-6), macrophage migration inhibitory factor (MIF) and other pro-inflammatory cytokines and reactive oxygen species (ROS), enhances the synthesis of endothelial nitric oxide (eNO), and anti-inflammatory cytokines interleukins-4 (IL-4) and interleukin-10 (IL-10). |
| 2668 | 17927013 | In subjects who are critically ill, monocyte HLA-DR expression was significantly decreased with a concomitant increase in plasma IL-10 and IL-4 concentrations. |
| 2669 | 17927013 | Large increases in the plasma concentrations of TNF-alpha, IL-6, sustained increase in the expression of leukocyte CD11b/CD18, and ROS generation following surgery and infections were found to be associated with increased mortality. |
| 2670 | 17949947 | The source of TcR was a CD4(+) T(H)1(+) T-cell clone which responded to an immunodominant epitope of the human islet protein GAD65, an epitope shared with both GAD65 and GAD67 in the mouse. |
| 2671 | 17949947 | The resulting HLA-DR4/GAD-TcR transgenic mice on a Rag2(o/o)/I-Ab(o/o)/B6 background exhibited a CD4(+) infiltrate into pancreatic islets that correlated with a loss of insulin in infiltrated islets. |
| 2672 | 17949947 | T cells containing the GAD65/67 (555-567) responsive TcR undergo strong negative selection as evidenced by a 10-fold lower thymocyte cellularity compared to non-TcR transgenic mice, and clonotype peripheral T cells represented approximately 1% of CD4(+) T cells in Rag2 sufficient mice. |
| 2673 | 17949947 | Upon in vitro stimulation, GAD65/67 555-567 responsive T cells secrete interferon-gamma, minimal interleukin (IL)-2 and tumor necrosis factor-alpha, and no IL-4, IL-5, IL-10, or IL-17, consistent with a T(H)1 profile. |
| 2674 | 17949947 | These data demonstrate that CD4(+) T cells specific for a naturally processed epitope within GAD can specifically home to pancreatic islets and lead to impaired islet beta-cell function in diabetes-associated HLA-DR4 transgenic mice on the relatively non-autoimmune C57BL/6 background. |
| 2675 | 17962984 | Patients with active tuberculosis were found to have lower IFNgamma levels and a higher production of other pro-inflammatory cytokines and IL-4, both in the presence and absence of diabetes. |
| 2676 | 17983440 | Intracellular staining revealed that these Th2 T-cell clones produce low levels of tumour necrosis factor-alpha (TNF-alpha) in vitro, and after adoptive transfer, they migrate to the pancreas where they produce TNF-alpha as well as Th2 cytokines (interleukin (IL)-4, IL-10). |
| 2677 | 18025164 | The therapeutic effect of transfused activated NOD B cells correlates closely with the observed decreased islet inflammation, reduced IFN-gamma production and increased production of IL-4 and IL-10 by splenocytes and CD4(+) T cells from NOD recipients of BCR-stimulated NOD B cells relative to splenocytes and CD4(+) T cells from PBS-treated control NOD mice. |
| 2678 | 18064633 | MIF deficiency resulted in lower proliferation and lymphocyte adhesion, as well as reduced production from the spleens and peritoneal cells of a variety of inflammatory mediators typically associated with development of the disease including IL-12, IL-23, TNF-alpha, and IL-1beta. |
| 2679 | 18064633 | Furthermore, MIF deletion affected the production of IL-18, TNF-alpha, IL-1beta, and iNOS in the islets of Langerhans. |
| 2680 | 18064633 | These data, along with the higher expression of IL-4 and TGF-beta observed in the periphery and in the pancreas of MLD-STZ-challenged MIF(-/-) mice as compared to WT controls suggest that MIF deficiency has induced an immune deviation towards protective type 2/3 response. |
| 2681 | 18091354 | We tested the hypothesis that formula feeding during the neonatal period accelerates the development of T1D in diabetes-prone BioBreeding (BBDP) rats through regulation of CD4+CD25+ regulatory T lymphocytes (T(reg)) and anti-inflammatory cytokines. |
| 2682 | 18091354 | The spleen and thymus were analyzed for Foxp3-expressing CD4+/CD25+ T cells. |
| 2683 | 18091354 | Multiplex enzyme-linked immunosorbent assays (ELISAs) were performed to measure cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, and IL-18. |
| 2684 | 18091354 | There were no differences in ileal cytokine concentrations of 75-d-old rats, but the formula-fed rats had greater liver TNF-alpha (p < 0.001), IFN-gamma, and IL-4 (p < 0.01) and lower IL-10 (p = 0.002) compared with MF animals. |
| 2685 | 18091354 | We tested the hypothesis that formula feeding during the neonatal period accelerates the development of T1D in diabetes-prone BioBreeding (BBDP) rats through regulation of CD4+CD25+ regulatory T lymphocytes (T(reg)) and anti-inflammatory cytokines. |
| 2686 | 18091354 | The spleen and thymus were analyzed for Foxp3-expressing CD4+/CD25+ T cells. |
| 2687 | 18091354 | Multiplex enzyme-linked immunosorbent assays (ELISAs) were performed to measure cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, and IL-18. |
| 2688 | 18091354 | There were no differences in ileal cytokine concentrations of 75-d-old rats, but the formula-fed rats had greater liver TNF-alpha (p < 0.001), IFN-gamma, and IL-4 (p < 0.01) and lower IL-10 (p = 0.002) compared with MF animals. |
| 2689 | 18178847 | Genome-wide microarray expression analysis of CD4+ T Cells from nonobese diabetic congenic mice identifies Cd55 (Daf1) and Acadl as candidate genes for type 1 diabetes. |
| 2690 | 18178847 | NOD.Idd3/5 congenic mice have insulin-dependent diabetes (Idd) regions on chromosomes 1 (Idd5) and 3 (Idd3) derived from the nondiabetic strains B10 and B6, respectively. |
| 2691 | 18178847 | To test the hypothesis that candidate Idd genes can be identified by differential gene expression between activated CD4+ T cells from the diabetes-susceptible NOD strain and the diabetes-resistant NOD.Idd3/5 congenic strain, genome-wide microarray expression analysis was performed using an empirical Bayes method. |
| 2692 | 18178847 | The two genes with the greatest differential RNA expression on chromosome 1 were those encoding decay-accelerating factor (DAF, also known as CD55) and acyl-coenzyme A dehydrogenase, long chain, which are located in the Idd5.4 and Idd5.3 regions, respectively. |
| 2693 | 18178847 | In the case of DAF, differential expression of mRNA was extended to the protein level; NOD CD4+ T cells expressed higher levels of cell surface DAF compared with NOD.Idd3/5 CD4+ T cells following activation with anti-CD3 and -CD28. |
| 2694 | 18178847 | DAF up-regulation was IL-4 dependent and blocked under Th1 conditions. |
| 2695 | 18230955 | They are clustered into three groups: noxious (the 'bad', 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the 'good', 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and 'aloof' , comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). |
| 2696 | 18230955 | IL-3 was reluctant to clustering and IL-30 through 33 were not included due to the scarce available data. |
| 2697 | 18271251 | Western blot showed that the expression product (SP(Usp45)-INS protein) targeted mainly at the cell wall while little was found in cytoplasm or supernatant. |
| 2698 | 18271251 | ELISA and Western blot results showed that the recombinant strain could induce SP(Usp45)-INS-specific antibodies and raise IL-4 level (38.583 +/- 2.083 pg/mL, P < 0.05) in the mice' s sera. |
| 2699 | 18318993 | The level of IFN-gamma was lower while IL-4 was higher in mDCs treated mice than that in umDCs treated mice, which indicated that Th1/Th2 deviation occurred. |
| 2700 | 18337172 | The protective effect of DC/IL-4 required both MHC and IL-4 expression by the DCs. |
| 2701 | 18338925 | The interleukins IL-2, IL-4, IL-10 and interferon gamma were quantified by ELISA. |
| 2702 | 18383559 | According to this concept, a T-helper lymphocyte of type 1 (Th1) subset of T-lymphocytes and their cytokine products, the type 1 cytokines [e.g. interleukin 2 (IL-2), interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF-beta)] prevail over immunoregulatory (anti-inflammatory) Th2 subset and its cytokine products, i.e. type 2 cytokines (e.g. |
| 2703 | 18383559 | IL-4, IL-6 and IL-10). |
| 2704 | 18383559 | Activation of sympathetic-corticotropin-releasing hormone (CRH) axis by psychological stress induces specifically Th1 cell overactivity that determines enhanced glutamine utilization and consequent poor L-arginine supply for nitric oxide (NO)-assisted insulin secretion. |
| 2705 | 18392872 | In this work, we assessed the in-vitro effects of eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) (final concentration, 15 microM) on T cell blastogenesis, interleukin-2 and -4 (IL-2, IL-4) secretion, fatty acid composition and intracellular oxidative status in type I diabetic patients with or without complications. |
| 2706 | 18392872 | EPA and DHA diminished T-lymphocyte proliferation and IL-2 production but enhanced IL-4 secretion in both diabetic and control groups. |
| 2707 | 18392872 | In this work, we assessed the in-vitro effects of eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) (final concentration, 15 microM) on T cell blastogenesis, interleukin-2 and -4 (IL-2, IL-4) secretion, fatty acid composition and intracellular oxidative status in type I diabetic patients with or without complications. |
| 2708 | 18392872 | EPA and DHA diminished T-lymphocyte proliferation and IL-2 production but enhanced IL-4 secretion in both diabetic and control groups. |
| 2709 | 18432585 | Plasma levels of Th1/Th2 type cytokine are associated with change of prolactin and GH/IGF-I in hemodialysis patients. |
| 2710 | 18432585 | The aims of the present study were to estimate the serum concentrations of Th1-Th2 cytokine, GH, insulin-like growth factor-I (IGF-I) and PRL, and to determine whether there are any correlations between the release of T-cell cytokines and disturbance of hormones in a group of patients on maintenance hemodialysis (MHD). |
| 2711 | 18432585 | Baseline serum concentrations of GH/IGF-I, PRL, IL-2, sIL-2R, IFN-gamma, IL-4 and IL-10 were measured in all patients and control subjects. |
| 2712 | 18432585 | Our results demonstrate that the fasting serum concentration of IGF-I, PRL, sIL-2R and Th1-type cytokine, including IL-2 and IFN-gamma, were significantly higher in HD patients compared to the healthy subjects. |
| 2713 | 18432585 | GH and Th2-type cytokine including IL-4 and IL-10 levels were slightly reduced, but no significant differences were observed between HD patients and the control group. |
| 2714 | 18432585 | In the group of HD patients, PRL correlated directly with IFN-gamma and correlated inversely with IL-10; IFN-gamma correlated inversely with IL-4; and GH also correlated inversely with IGF-I and IL-4. |
| 2715 | 18432585 | However, IGF-I correlated directly with IL-2 and IL-10. |
| 2716 | 18432585 | These data suggest that the Th1/Th2 imbalance in HD patients with an increase of Th1 type cytokines, associated with the altered GH/IGF-I axis and prolactin and immuno-endocrine dysfunction, probably plays a role in an impaired immune system in HD patients. |
| 2717 | 18432585 | Plasma levels of Th1/Th2 type cytokine are associated with change of prolactin and GH/IGF-I in hemodialysis patients. |
| 2718 | 18432585 | The aims of the present study were to estimate the serum concentrations of Th1-Th2 cytokine, GH, insulin-like growth factor-I (IGF-I) and PRL, and to determine whether there are any correlations between the release of T-cell cytokines and disturbance of hormones in a group of patients on maintenance hemodialysis (MHD). |
| 2719 | 18432585 | Baseline serum concentrations of GH/IGF-I, PRL, IL-2, sIL-2R, IFN-gamma, IL-4 and IL-10 were measured in all patients and control subjects. |
| 2720 | 18432585 | Our results demonstrate that the fasting serum concentration of IGF-I, PRL, sIL-2R and Th1-type cytokine, including IL-2 and IFN-gamma, were significantly higher in HD patients compared to the healthy subjects. |
| 2721 | 18432585 | GH and Th2-type cytokine including IL-4 and IL-10 levels were slightly reduced, but no significant differences were observed between HD patients and the control group. |
| 2722 | 18432585 | In the group of HD patients, PRL correlated directly with IFN-gamma and correlated inversely with IL-10; IFN-gamma correlated inversely with IL-4; and GH also correlated inversely with IGF-I and IL-4. |
| 2723 | 18432585 | However, IGF-I correlated directly with IL-2 and IL-10. |
| 2724 | 18432585 | These data suggest that the Th1/Th2 imbalance in HD patients with an increase of Th1 type cytokines, associated with the altered GH/IGF-I axis and prolactin and immuno-endocrine dysfunction, probably plays a role in an impaired immune system in HD patients. |
| 2725 | 18432585 | Plasma levels of Th1/Th2 type cytokine are associated with change of prolactin and GH/IGF-I in hemodialysis patients. |
| 2726 | 18432585 | The aims of the present study were to estimate the serum concentrations of Th1-Th2 cytokine, GH, insulin-like growth factor-I (IGF-I) and PRL, and to determine whether there are any correlations between the release of T-cell cytokines and disturbance of hormones in a group of patients on maintenance hemodialysis (MHD). |
| 2727 | 18432585 | Baseline serum concentrations of GH/IGF-I, PRL, IL-2, sIL-2R, IFN-gamma, IL-4 and IL-10 were measured in all patients and control subjects. |
| 2728 | 18432585 | Our results demonstrate that the fasting serum concentration of IGF-I, PRL, sIL-2R and Th1-type cytokine, including IL-2 and IFN-gamma, were significantly higher in HD patients compared to the healthy subjects. |
| 2729 | 18432585 | GH and Th2-type cytokine including IL-4 and IL-10 levels were slightly reduced, but no significant differences were observed between HD patients and the control group. |
| 2730 | 18432585 | In the group of HD patients, PRL correlated directly with IFN-gamma and correlated inversely with IL-10; IFN-gamma correlated inversely with IL-4; and GH also correlated inversely with IGF-I and IL-4. |
| 2731 | 18432585 | However, IGF-I correlated directly with IL-2 and IL-10. |
| 2732 | 18432585 | These data suggest that the Th1/Th2 imbalance in HD patients with an increase of Th1 type cytokines, associated with the altered GH/IGF-I axis and prolactin and immuno-endocrine dysfunction, probably plays a role in an impaired immune system in HD patients. |
| 2733 | 18435801 | Because the role of regulatory T cells in the intestinal inflammation is unknown in coeliac disease (CD) and type 1 diabetes (T1D), the expression of forkhead box P3 (FoxP3), CD25, transforming growth factor-beta, interferon (IFN)-gamma, interleukin (IL)-4, IL-8, IL-10, IL-15 and IL-18 was measured by quantitative reverse transcription-polymerase chain reaction in the small intestinal biopsies from paediatric patients with active or potential CD, T1D and control patients. |
| 2734 | 18435801 | Enhanced intestinal expressions of FoxP3, IL-10 and IFN-gamma mRNAs were found in active CD when compared with controls (P-values < 0.001, 0.004, <0.001). |
| 2735 | 18435801 | The ratio of IFN-gamma to FoxP3-specific mRNA was increased in active and potential CD (P = 0.001 and P = 0.002). |
| 2736 | 18435801 | The increased ratio of IFN-gamma to FoxP3 mRNA in active and potential CD suggests an imbalance between regulatory and effector mechanisms. |
| 2737 | 18522831 | Here we show that in response to the Th2 cytokine interleukin-4 (IL-4), peroxisome proliferator-activated receptor delta (PPARdelta) directs expression of the alternative phenotype in Kupffer cells and adipose tissue macrophages of lean mice. |
| 2738 | 18522831 | However, adoptive transfer of PPARdelta(-/-) (Ppard(-/-)) bone marrow into wild-type mice diminishes alternative activation of hepatic macrophages, causing hepatic dysfunction and systemic insulin resistance. |
| 2739 | 18560422 | Moreover, expression of mIL-4 also maintained the level of CD4(+)CD25(+)FoxP3(+) cells, and adoptive transfer of splenocytes from nondiabetic dsAAV8-mIP-IL-4 mice to NODscid mice was able to block the diabetes induced by splenocytes co-adoptively transferred from nondiabetic dsAAV-mIP-eGFP mice. |
| 2740 | 18562629 | INO-2002 treatment decreased pancreatic levels of interleukin (IL)-12 and tumour necrosis factor-alpha, while increasing levels of IL-4 and IL-10. |
| 2741 | 18562629 | INO-2002 also reduced pancreatic levels of the chemokine MIP-1 alpha. |
| 2742 | 18606638 | Impaired SLAM-SLAM homotypic interaction between invariant NKT cells and dendritic cells affects differentiation of IL-4/IL-10-secreting NKT2 cells in nonobese diabetic mice. |
| 2743 | 18606638 | The regulatory function of invariant NKT (iNKT) cells for tolerance induction and prevention of autoimmunity is linked to a specific cytokine profile that comprises the secretion of type 2 cytokines like IL-4 and IL-10 (NKT2 cytokine profile). |
| 2744 | 18606638 | In contrast, mature NOD mDC express significantly lower levels of SLAM and are unable to promote GATA-3 (the SLAM-induced intracellular signal) up-regulation and IL-4/IL-10 production in iNKT cells from NOD or C57BL/6 mice. |
| 2745 | 18606638 | Impaired SLAM-SLAM homotypic interaction between invariant NKT cells and dendritic cells affects differentiation of IL-4/IL-10-secreting NKT2 cells in nonobese diabetic mice. |
| 2746 | 18606638 | The regulatory function of invariant NKT (iNKT) cells for tolerance induction and prevention of autoimmunity is linked to a specific cytokine profile that comprises the secretion of type 2 cytokines like IL-4 and IL-10 (NKT2 cytokine profile). |
| 2747 | 18606638 | In contrast, mature NOD mDC express significantly lower levels of SLAM and are unable to promote GATA-3 (the SLAM-induced intracellular signal) up-regulation and IL-4/IL-10 production in iNKT cells from NOD or C57BL/6 mice. |
| 2748 | 18606638 | Impaired SLAM-SLAM homotypic interaction between invariant NKT cells and dendritic cells affects differentiation of IL-4/IL-10-secreting NKT2 cells in nonobese diabetic mice. |
| 2749 | 18606638 | The regulatory function of invariant NKT (iNKT) cells for tolerance induction and prevention of autoimmunity is linked to a specific cytokine profile that comprises the secretion of type 2 cytokines like IL-4 and IL-10 (NKT2 cytokine profile). |
| 2750 | 18606638 | In contrast, mature NOD mDC express significantly lower levels of SLAM and are unable to promote GATA-3 (the SLAM-induced intracellular signal) up-regulation and IL-4/IL-10 production in iNKT cells from NOD or C57BL/6 mice. |
| 2751 | 18641312 | In parallel, the production of IL-4 and IFN-gamma following alpha-GalCer stimulation was proportionally reduced. |
| 2752 | 18675592 | Whereas intramuscular injection of pGAD65 promoted a predominant type 1 CD4(+) T cell response and failed to suppress ongoing beta cell autoimmunity, gene gun vaccination preferentially induced IL-4 secreting CD4(+) T cells and significantly delayed the onset of diabetes. |
| 2753 | 18716002 | Moreover, blockade of IFN-alpha receptor 1 in NOD mice by a neutralizing antibody at 2-3 weeks of age significantly delayed the onset and decreased the incidence of type 1 diabetes, increased the relative number of immature dendritic cells in the PLNs, and enhanced the ability of spleen CD4(+) T cells to produce IL-4 and IL-10. |
| 2754 | 18725525 | Dicer-deficient T reg lineage cells failed to remain stable, as a subset of cells down-regulated the T reg cell-specific transcription factor FoxP3, whereas the majority expressed altered levels of multiple genes and proteins (including Neuropilin 1, glucocorticoid-induced tumor necrosis factor receptor, and cytotoxic T lymphocyte antigen 4) associated with the T reg cell fingerprint. |
| 2755 | 18725525 | In fact, a significant percentage of the T reg lineage cells took on a T helper cell memory phenotype including increased levels of CD127, interleukin 4, and interferon gamma. |
| 2756 | 18778952 | Four weeks later, splenocytes were harvested, mitogen stimulated, and analyzed for cytokine production (IL-2, IL-4, and IL-10) along with stimulation indices (SI). |
| 2757 | 18778952 | Stimulated IL-10 concentrations were elevated in STZ-treated CFTR-/- compared to LR-treated animals and controls (p<0.05). |
| 2758 | 18778952 | IL-2 levels were greater in CFTR-/- mice compared to controls (p<0.05), but unrelated to STZ. |
| 2759 | 18778952 | Reinforcing generalized cytokine up-regulation in CFTR-/-, IL-4 levels were greater in CFTR-/- mice compared to C57BL/6J, but FVB/NJ mice demonstrated greatest concentrations following STZ. |
| 2760 | 18778952 | Four weeks later, splenocytes were harvested, mitogen stimulated, and analyzed for cytokine production (IL-2, IL-4, and IL-10) along with stimulation indices (SI). |
| 2761 | 18778952 | Stimulated IL-10 concentrations were elevated in STZ-treated CFTR-/- compared to LR-treated animals and controls (p<0.05). |
| 2762 | 18778952 | IL-2 levels were greater in CFTR-/- mice compared to controls (p<0.05), but unrelated to STZ. |
| 2763 | 18778952 | Reinforcing generalized cytokine up-regulation in CFTR-/-, IL-4 levels were greater in CFTR-/- mice compared to C57BL/6J, but FVB/NJ mice demonstrated greatest concentrations following STZ. |
| 2764 | 18797414 | This pattern was also observed in other immunomodulatory factors (notably cortisol and epidermal growth factor), while (interleukin [IL]-1alpha, IL-4, IL-6, IL-9, IL-10, TNF-alpha, Eotaxin) did not change significantly. |
| 2765 | 18850043 | EEPHC significantly suppressed the expression of major histocompatibility complex (MHC) class II molecules and the costimulatory molecules CD40 and CD86 in NOD BM-DCs. |
| 2766 | 18850043 | Furthermore, splenocytes from the protected mice produced high amounts of IL-4 and IL-10 and low levels of IL-2 and interferon gamma, suggesting that these DCs deficient in NF- kappaB activity are responsible for the apparent shift in type 2 helper T cells. |
| 2767 | 18931971 | Furthermore, IL-27 up-regulated pro-inflammatory cytokines IFN-gamma and IL-17 and down-regulated anti-inflammatory cytokines IL-4, TGF-beta, and IL-10 secreted by diabetic splenocytes. |
| 2768 | 18940257 | In particular, the ability of certain cytokines, for example, IL-2, to provide vital survival signals to regulatory cells and to trigger death of effector T cells or impede IL-15 driven expansion of memory cells has spurred several trials. |
| 2769 | 18940257 | The ability of IFNgamma, IL-4, TNFalpha, and lymphotoxin to exert selective effects upon crucial lymphocyte subset populations in vivo may also enable translation into potent therapies. |
| 2770 | 19006694 | CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. |
| 2771 | 19006694 | We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. |
| 2772 | 19006694 | These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. |
| 2773 | 19026451 | Potential diabetes susceptibility genes include immuno-regulatory TH1/TH2 cytokines such as IFNgamma, IL-12, IL-4 and IL-10. |
| 2774 | 19026451 | When SNPs were examined for an association with diabetes by case:control analysis significant associations were observed for IL-4 in three breeds, the Collie, Cairn Terrier and Schnauzer and for IL-10 in the Cavalier King Charles Spaniel. |
| 2775 | 19026451 | Potential diabetes susceptibility genes include immuno-regulatory TH1/TH2 cytokines such as IFNgamma, IL-12, IL-4 and IL-10. |
| 2776 | 19026451 | When SNPs were examined for an association with diabetes by case:control analysis significant associations were observed for IL-4 in three breeds, the Collie, Cairn Terrier and Schnauzer and for IL-10 in the Cavalier King Charles Spaniel. |
| 2777 | 19120317 | Multiple studies have shown that thymus-derived naturally occurring Tregs constitutively express the forkhead/winged helix transcription factor FoxP3 in addition to high levels of CD25, the negative co-stimulatory molecule CTLA-4, and the glucocorticoid-induced TNF receptor-related protein GITR. |
| 2778 | 19120317 | At variance, adaptive or induced Tregs acquire these phenotypic markers as they differentiate in the periphery, following adequate stimulation in the appropriate environment, together with their capacity to produce immunomodulatory cytokines (mainly, IL-4, IL-10 and TGF-beta) and to display regulatory capacities. |
| 2779 | 19120317 | Moreover, data are presented that simultaneous blockade of CTLA4 and TGF-beta further impairs immunoregulatory circuits that control disease progression. |
| 2780 | 19188932 | Induction of CD4+CD25+Foxp3+ regulatory T cell response by glatiramer acetate in type 1 diabetes. |
| 2781 | 19188932 | Treatment with GA significantly reduced the diabetic rate in the mice and ameliorated insulitis, which coincided with increased CD4+CD25+Foxp3+ T cell response in treated mice. |
| 2782 | 19188932 | IL-4 was found to maintain Foxp3 expression and regulatory function of CD4+CD25+ regulatory T cells (Tregs). |
| 2783 | 19224710 | A profound and progressive infiltration with CD4(+), CD8(+) cells, natural killer cells, and macrophages was identified in adenovirus transduced grafts, which paralleled a decline in beta-gal expression. |
| 2784 | 19224710 | Intragraft interferon (IFN)-gamma and RANTES mRNA expression was not different between transduced and untransduced islet grafts, despite an increased expression of CC chemokine receptor 5 (CCR5). |
| 2785 | 19224710 | No significant splenocyte IFN-gamma and interleukin (IL)-4 production or serum anti-adenoviral antibodies were discovered albeit IgM antibody was detected in transduced grafts. |
| 2786 | 19234158 | We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount of Th1 cells, augments the number of T cells secreting IL-4 or IL-10 specific for islet cell Ag, and causes peripheral deletion of beta-cell-reactive T cells. |
| 2787 | 19234158 | Preventive gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets and that contained a significantly reduced number of Th1 cells and a higher percentage of CD4(+) T cells with content of IL-4, IL-5, or IL-10. |
| 2788 | 19234158 | We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount of Th1 cells, augments the number of T cells secreting IL-4 or IL-10 specific for islet cell Ag, and causes peripheral deletion of beta-cell-reactive T cells. |
| 2789 | 19234158 | Preventive gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets and that contained a significantly reduced number of Th1 cells and a higher percentage of CD4(+) T cells with content of IL-4, IL-5, or IL-10. |
| 2790 | 19361556 | The expression of mRNA coding IFN-gamma was lower but that of IL-4 was higher in B7-H4-NIT transplanted recipients than in the control animals. |
| 2791 | 19557358 | At the cell level, the hexane fraction markedly inhibited beta-hexosaminidase release from RBL-2H3 mast cells and suppressed the expressions of mRNA interferon-gamma and interleukin-4 cytokines produced by T helper cells (type 1 and 2). |
| 2792 | 19752032 | Helminth infection can reduce insulitis and type 1 diabetes through CD25- and IL-10-independent mechanisms. |
| 2793 | 19752032 | Interleukin-4 (IL-4), IL-10, and IL-13 expression and the frequency of CD4(+) CD25(+) FoxP3(+) regulatory T cells were elevated in mesenteric and pancreatic lymph nodes. |
| 2794 | 19752032 | Depletion of CD4(+) CD25(+) T cells in vivo did not abrogate H. polygyrus-induced T1D protection, nor did anti-IL-10 receptor blocking antibody. |
| 2795 | 19752032 | These findings suggest that infection with H. polygyrus significantly inhibits T1D in NOD mice through CD25- and IL-10-independent mechanisms and also reduces the severity of T1D when administered late after the onset of insulitis. |
| 2796 | 19855244 | Treatment group showed increased serum interleukin (IL)-10 (twofold) and decreased inducible protein-10 and IL-4 (threefold) in luminex. |
| 2797 | 19855244 | Significantly reduced frequency of interferon-gamma (4.5-fold), IL-4 (3.5-fold), IL-2 (2.3-fold), and IL-17 (fourfold) producing T-cell populations were found in ELISPOT. |
| 2798 | 19855244 | OA-treated grafts had significant reduced and delayed infiltration of CD4+ and CD8+ T cells. |
| 2799 | 19855244 | Treatment group showed increased serum interleukin (IL)-10 (twofold) and decreased inducible protein-10 and IL-4 (threefold) in luminex. |
| 2800 | 19855244 | Significantly reduced frequency of interferon-gamma (4.5-fold), IL-4 (3.5-fold), IL-2 (2.3-fold), and IL-17 (fourfold) producing T-cell populations were found in ELISPOT. |
| 2801 | 19855244 | OA-treated grafts had significant reduced and delayed infiltration of CD4+ and CD8+ T cells. |
| 2802 | 19886740 | Unexpectedly, the ratio of CD4(+):CD8(+) T cells was tightly controlled in the islets throughout diabetogenesis. |
| 2803 | 19886740 | The frequency of IL-4(+) CD4(+) T cells started high but quickly fell to 3% of the population that was maintained with increasing inflammation. |
| 2804 | 19886740 | A significant portion of the CD8(+) T cells were islet-specific glucose-6-phosphatase catalytic subunit-related protein specific in both male and female NOD mice and this population was antigen experienced and increased at high levels of islet inflammation. |
| 2805 | 19956098 | Individual SNPs and SNP haplotypes in IL4R, which encodes the alpha-chain of the IL4 and IL13 receptors, have been associated with T1D in some reports, but not in others. |
| 2806 | 20069130 | Infected mice that received MLDS did not show an increase in their regulatory T cell population, however, they had a greater number of alternatively activated macrophages, higher levels of the cytokine IL-4, and lower levels of TNF-alpha. |
| 2807 | 20359955 | Splenocytes of NOD mice immunized with this peptide secreted IL-4 and IL-10 in response to L7-24. |
| 2808 | 20364398 | VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population. |
| 2809 | 20364398 | In this study, we have analyzed the effect of 1154 A/G polymorphism of VEGF and 70 bp VNTR polymorphism of intron 3 in IL-4 genes in coronary heart disease (CHD) patients (n = 300) and their age matched controls (n = 300). |
| 2810 | 20364398 | GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes. |
| 2811 | 20364398 | VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population. |
| 2812 | 20364398 | In this study, we have analyzed the effect of 1154 A/G polymorphism of VEGF and 70 bp VNTR polymorphism of intron 3 in IL-4 genes in coronary heart disease (CHD) patients (n = 300) and their age matched controls (n = 300). |
| 2813 | 20364398 | GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes. |
| 2814 | 20364398 | VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population. |
| 2815 | 20364398 | In this study, we have analyzed the effect of 1154 A/G polymorphism of VEGF and 70 bp VNTR polymorphism of intron 3 in IL-4 genes in coronary heart disease (CHD) patients (n = 300) and their age matched controls (n = 300). |
| 2816 | 20364398 | GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes. |
| 2817 | 20371733 | Intracerebroventricular pretreatment with PS1145, an inhibitor of IKKbeta (a key intracellular mediator of inflammatory signaling), blocked both IL-4 effects, suggesting a causal relationship between IL-4-induced weight gain and hypothalamic inflammation. |
| 2818 | 20406305 | In this study we show that the PPARdelta agonists GW501516 and L165041 ameliorate MOGp35-55-induced EAE in C57BL/6 mice by blocking interferon (IFN)-gamma and interleukin (IL)-17 production by T helper type 1 (Th1) and Th17 cells. |
| 2819 | 20406305 | The inhibition of EAE by PPARdelta agonists was also associated with a decrease in IL-12 and IL-23 and an increase in IL-4 and IL-10 expression in the CNS and lymphoid organs. |
| 2820 | 20406664 | Increased anti-GAD65 IgG1, serum IgA and unchanged IgG2a antibodies titers; together with an increase of IL-4, IL-10 production and a decrease of IFN-gamma production suggested possible activation of GAD65-specific Th2 immune responses. |
| 2821 | 20498357 | Here we report that IL-9 is secreted by human naive CD4 T cells in response to differentiation by Th9 (TGF-beta and IL-4) or Th17 polarizing conditions. |
| 2822 | 20498357 | Yet, these differentiated naive cells did not coexpress IL-17 and IL-9, unless they were repeatedly stimulated under Th17 differentiation-inducing conditions. |
| 2823 | 20498357 | In contrast to the naive cells, memory CD4 T cells were induced to secrete IL-9 by simply providing TGF-beta during stimulation, as neither IL-4 nor proinflammatory cytokines were required. |
| 2824 | 20498357 | Furthermore, the addition of TGF-beta to the Th17-inducing cytokines (IL-1beta, IL-6, IL-21, IL-23) that induce memory cells to secrete IL-17, resulted in the marked coexpression of IL-9 in IL-17 producing memory cells. |
| 2825 | 20498357 | The proinflammatory cytokine mediating TGF-beta-dependent coexpression of IL-9 and IL-17 was identified to be IL-1beta. |
| 2826 | 20498357 | Moreover, circulating monocytes were potent costimulators of IL-9 production by Th17 cells via their capacity to secrete IL-1beta. |
| 2827 | 20498357 | Finally, to determine whether IL-9/IL-17 coproducing CD4 cells were altered in an inflammatory condition, we examined patients with autoimmune diabetes and demonstrated that these subjects exhibit a higher frequency of memory CD4 cells with the capacity to transition into IL-9(+)IL-17(+) cells. |
| 2828 | 20498357 | These data demonstrate the presence of IL-17(+)IL-9(+) CD4 cells induced by IL-1beta that may play a role in human autoimmune disease. |
| 2829 | 20498357 | Here we report that IL-9 is secreted by human naive CD4 T cells in response to differentiation by Th9 (TGF-beta and IL-4) or Th17 polarizing conditions. |
| 2830 | 20498357 | Yet, these differentiated naive cells did not coexpress IL-17 and IL-9, unless they were repeatedly stimulated under Th17 differentiation-inducing conditions. |
| 2831 | 20498357 | In contrast to the naive cells, memory CD4 T cells were induced to secrete IL-9 by simply providing TGF-beta during stimulation, as neither IL-4 nor proinflammatory cytokines were required. |
| 2832 | 20498357 | Furthermore, the addition of TGF-beta to the Th17-inducing cytokines (IL-1beta, IL-6, IL-21, IL-23) that induce memory cells to secrete IL-17, resulted in the marked coexpression of IL-9 in IL-17 producing memory cells. |
| 2833 | 20498357 | The proinflammatory cytokine mediating TGF-beta-dependent coexpression of IL-9 and IL-17 was identified to be IL-1beta. |
| 2834 | 20498357 | Moreover, circulating monocytes were potent costimulators of IL-9 production by Th17 cells via their capacity to secrete IL-1beta. |
| 2835 | 20498357 | Finally, to determine whether IL-9/IL-17 coproducing CD4 cells were altered in an inflammatory condition, we examined patients with autoimmune diabetes and demonstrated that these subjects exhibit a higher frequency of memory CD4 cells with the capacity to transition into IL-9(+)IL-17(+) cells. |
| 2836 | 20498357 | These data demonstrate the presence of IL-17(+)IL-9(+) CD4 cells induced by IL-1beta that may play a role in human autoimmune disease. |
| 2837 | 20529823 | The aim of our study was to test the hypothesis that T regulatory cells express pro- and anti-inflammatory cytokines, elements of cytotoxicity and OX40/4-1BB molecules. |
| 2838 | 20529823 | Concurrently with the flow cytometric assessment of Tregs we separated CD4+CD25+CD127dim/- cells for further mRNA analysis. mRNA levels for transcription factor FoxP3, pro- and anti-inflammatory cytokines (interferon gamma, interleukin-2, interleukin-4, interleukin-10, transforming growth factor beta1 and tumor necrosis factor alpha), activatory molecules (OX40, 4-1BB) and elements of cytotoxicity (granzyme B, perforin 1) were determined by real-time PCR technique. |
| 2839 | 20529823 | Lower OX40 and higher 4-1BB mRNA but not protein levels in Treg cells in diabetic patients compared to the healthy children were noted. |
| 2840 | 20529823 | Our observations confirm the presence of mRNA for pro- and anti-inflammatory cytokines in CD4+CD25+CD127dim/- cells in the peripheral blood of children with T1DM. |
| 2841 | 20674317 | The pro-inflammatory cytokines, IL-1 and TNFα, as well as the Th1 cytokines, IL-2 and IFNγ were more elevated in female NOD mice whereas the Th2 cytokine, IL-4, was more depressed in these mice compared to their male counterparts. |
| 2842 | 20703434 | Differential effects of cytokines IFN-gamma and IL-4 in the development of inflammatory macrophages, and the distinct developmental pathways of proinflammatory or tissue-repair-associated monocytes suggest that controlling the activity of these monocytes could be part of an immune intervention strategy to prevent T1D. |
| 2843 | 20703439 | The ability of encapsulated islets to survive in this mouse model might partly be attributed to the presence of Th2 cytokines IL-4 and IL-10, which are known to induce graft tolerance. |
| 2844 | 20703439 | As another result, the maintained viability of transplanted islets on the NOD/SCID background emphasized a critical role of protective mechanisms in autoimmune diabetes transplanted subjects due to specific immunoregulatory effects provided by IL-4 and IL-10. |
| 2845 | 20703439 | The ability of encapsulated islets to survive in this mouse model might partly be attributed to the presence of Th2 cytokines IL-4 and IL-10, which are known to induce graft tolerance. |
| 2846 | 20703439 | As another result, the maintained viability of transplanted islets on the NOD/SCID background emphasized a critical role of protective mechanisms in autoimmune diabetes transplanted subjects due to specific immunoregulatory effects provided by IL-4 and IL-10. |
| 2847 | 21050716 | To this end, we determined the feasibility of cloning and expanding human CD4(+) Treg specific for the type 1 diabetes autoantigens, GAD65 and proinsulin. |
| 2848 | 21050716 | Blood CD4(+) cells stimulated to divide in response to GAD65 (in three healthy individuals) or proinsulin (in one type 1 diabetic) were flow sorted into single cells and cultured on feeder cells in the presence of anti-CD3 monoclonal antibody, IL-2 and IL-4. |
| 2849 | 21050716 | Treg clones were not distinguished by markers of conventional CD4(+)CD25(+) Treg and suppressed independently of cell-cell contact but not via known soluble suppressor factors. |
| 2850 | 21127885 | Serum concentrations of interleukin-4 and interferon-gamma in relation to severe left ventricular dysfunction in patients with acute myocardial infarction undergoing percutaneous coronary intervention. |
| 2851 | 21321581 | Protection against diabetes was accompanied by histone hyperacetylation in pancreas and spleen, enhanced frequency of CD4(+) CD62L(+) cells in the spleen, reduction in cellular infiltration of islets, restoration of normoglycemia and glucose-induced insulin release by beta cells. |
| 2852 | 21321581 | Activation of splenic T lymphocytes derived from protected mice in vitro with pharmacological agents that bypass the antigen receptor or immobilized anti-CD3 antibody resulted in enhanced expression of Ifng mRNA and protein without altering the expression of Il4, Il17, Il18, Inos and Tnfa genes nor the secretion of IL-2, IL-4, IL-17 and TNF-α proteins. |
| 2853 | 21321581 | Consistently, expression of the transcription factor involved in Ifng transcription, Tbet/Tbx21 but not Gata3 and Rorgt, respectively, required for the transcription of Il4 and Il17, was upregulated in activated splenocytes of protected mice. |
| 2854 | 21321581 | Protection against diabetes was accompanied by histone hyperacetylation in pancreas and spleen, enhanced frequency of CD4(+) CD62L(+) cells in the spleen, reduction in cellular infiltration of islets, restoration of normoglycemia and glucose-induced insulin release by beta cells. |
| 2855 | 21321581 | Activation of splenic T lymphocytes derived from protected mice in vitro with pharmacological agents that bypass the antigen receptor or immobilized anti-CD3 antibody resulted in enhanced expression of Ifng mRNA and protein without altering the expression of Il4, Il17, Il18, Inos and Tnfa genes nor the secretion of IL-2, IL-4, IL-17 and TNF-α proteins. |
| 2856 | 21321581 | Consistently, expression of the transcription factor involved in Ifng transcription, Tbet/Tbx21 but not Gata3 and Rorgt, respectively, required for the transcription of Il4 and Il17, was upregulated in activated splenocytes of protected mice. |
| 2857 | 21346228 | Typical Th2 cytokines such as IL-10 or IL-4 were undetectable in 2.5mi(+) T cells, arguing against a mechanism of immune deviation. |
| 2858 | 21431832 | Several proinflammatory cytokines, acute-phase proteins, and cell adhesion molecules, such as C-reactive protein (CRP), interleukines (IL), and tumor necrosis factor alpha (TNF-α), seem to play a role in the low-grade systemic inflammation observed in these subjects. |
| 2859 | 21431832 | Recent research showed that combined exercise has greater anti-inflammatory effects than aerobic or resistance exercise alone causing a deepest decrease in CRP, IL-6, IL-1β, TNF-α, leptin, and resistin and a higher increase in anti-inflammatory cytokines such as IL-4, IL-10, and adiponectin. |
| 2860 | 21458378 | The suppression was likely to be mediated by T cells, as we found that regulatory CD4(+)CD25(+)Foxp3(+) cells were significantly increased in G/10-DC treated animals. |
| 2861 | 21458378 | In vivo, the G/10-DCs inhibited diabetogenic T cell proliferation; in vitro, they had reduced expression of costimulatory molecules and produced little IL-12/23 p40 or IL-6 but a large amount of IL-10 when compared with DCs matured in the presence of IL-4 (G/4-DC). |
| 2862 | 21593413 | IL-21 is a pleiotropic type 1 cytokine that shares the common cytokine receptor γ-chain, γ(c), with IL-2, IL-4, IL-7, IL-9, and IL-15. |
| 2863 | 21593413 | IL-21 is most homologous to IL-2. |
| 2864 | 21593413 | Whereas IL-2 promotes development of regulatory T cells and confers protection from autoimmune disease, IL-21 promotes differentiation of Th17 cells and is implicated in several autoimmune diseases, including type 1 diabetes and systemic lupus erythematosus. |
| 2865 | 21593413 | However, the roles of IL-21 and IL-2 in CNS autoimmune diseases such as multiple sclerosis and uveitis have been controversial. |
| 2866 | 21593413 | Here, we generated Il21-mCherry/Il2-emGFP dual-reporter transgenic mice and showed that development of experimental autoimmune uveitis (EAU) correlated with the presence of T cells coexpressing IL-21 and IL-2 into the retina. |
| 2867 | 21636855 | p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages. |
| 2868 | 21636855 | Transcriptome analysis revealed that p16(-/-) BM-derived macrophages (BMDMs) exhibit a phenotype resembling IL-4-induced macrophage polarization. |
| 2869 | 21636855 | In line with this observation, p16(-/-) BMDMs displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. |
| 2870 | 21636855 | Surprisingly, p16(-/-) BMDMs did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and lipopolysaccharide (LPS)-induced IKKα,β phosphorylation. |
| 2871 | 21636855 | This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. |
| 2872 | 21636855 | p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages. |
| 2873 | 21636855 | Transcriptome analysis revealed that p16(-/-) BM-derived macrophages (BMDMs) exhibit a phenotype resembling IL-4-induced macrophage polarization. |
| 2874 | 21636855 | In line with this observation, p16(-/-) BMDMs displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. |
| 2875 | 21636855 | Surprisingly, p16(-/-) BMDMs did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and lipopolysaccharide (LPS)-induced IKKα,β phosphorylation. |
| 2876 | 21636855 | This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. |
| 2877 | 21636855 | p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages. |
| 2878 | 21636855 | Transcriptome analysis revealed that p16(-/-) BM-derived macrophages (BMDMs) exhibit a phenotype resembling IL-4-induced macrophage polarization. |
| 2879 | 21636855 | In line with this observation, p16(-/-) BMDMs displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. |
| 2880 | 21636855 | Surprisingly, p16(-/-) BMDMs did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and lipopolysaccharide (LPS)-induced IKKα,β phosphorylation. |
| 2881 | 21636855 | This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. |
| 2882 | 21636855 | p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages. |
| 2883 | 21636855 | Transcriptome analysis revealed that p16(-/-) BM-derived macrophages (BMDMs) exhibit a phenotype resembling IL-4-induced macrophage polarization. |
| 2884 | 21636855 | In line with this observation, p16(-/-) BMDMs displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. |
| 2885 | 21636855 | Surprisingly, p16(-/-) BMDMs did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and lipopolysaccharide (LPS)-induced IKKα,β phosphorylation. |
| 2886 | 21636855 | This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. |
| 2887 | 21647406 | DCs play a crucial role in the presentation of autoantigen and activation of diabetogenic T cells, and IRF4 and IRF8 are crucial genes involved in the development of DCs. |
| 2888 | 21647406 | Importantly, levels of IRF4 and IRF8 expression were lower in tolerogenic bone marrow derived DCs (BMDCs) generated with GM-CSF as compared to immunogenic BMDCs generated with GM-CSF and IL-4. |
| 2889 | 21647406 | Analysis of splenic DCs subsets indicated that high expression of IRF4 was associated with increased levels of CD4(+)CD8α(-)IRF4(+)CD11c(+) DCs but not CD4(-)CD8α(+)IRF8(+)CD11c(+) DCs in NOD mice. |
| 2890 | 21647406 | Our results showed that IRF4 expression was up-regulated in NOD mice and correlated with the increased levels of CD4(+)CD8α(-) DCs, suggesting that IRF4 may be involved in abnormal DC functions in type 1 diabetes in NOD mice. |
| 2891 | 21678423 | We found that F4/80(+) peritoneal exudate macrophages (PEMs) from mice with diabetes for 4 months displayed significantly reduced CD86 and CD54 expression and tumor necrosis factor (TNF)-α and IL-6 production but enhanced nitric oxide (NO) secretion compared with control mice when treated with interferon (IFN)-γ and lipopolysaccharide (LPS), while the activity of arginase in PEMs from diabetic mice was significantly higher than control mice when stimulating with IL-4. |
| 2892 | 21678423 | In an in vitro culture system, high glucose and insulin significantly altered TNF-α, IL-6, and NO production and arginase activity of macrophages, which was reversed by the treatment with AKT and ERK inhibitors. |
| 2893 | 21708950 | HDAC9 deficiency also resulted in increased GATA3 and roquin and decreased BCL6 gene expression. |
| 2894 | 21708950 | HDAC9 deficiency was associated with increased site-specific lysine histone acetylation at H3 (H3K9, H3K14, and H3K18) globally that was localized to IL-4, roquin, and peroxisome proliferator-activated receptor-γ promoters with increased gene expression, respectively. |
| 2895 | 21717080 | The protective effect, as a result of vaccination, correlated with an increase in the levels of IL-10 and IL-4 cytokines as well as a skewing to Th2-dependent isotype antibodies in serum. |
| 2896 | 21724337 | Human pathogenesis of VL and reduced levels of leptin both are associated with increase in Th2 type immune response, characterized by secretion of cytokines such as IL-4 and IL-10. |
| 2897 | 21724337 | Whereas, the protective immune response during visceral leishmaniasis is associated with effective Th1 type immune response characterized by secretion of IFN-γ, IL-2 and IL-12, which correlates with leptin induction of T cells polarizing to Th1 population and secretion of proinflammatory cytokines, and also inhibition of Th2 type response. |
| 2898 | 21780542 | By measuring the values of TNF-a, fibrinogen, high sensitive capsule reactive protein (hs-CRP), IL-4, IL-6, IL-8, IL-10, at the beginning of non-surgical periodontal therapy and it has been after 3 months of treatment, noticed a relevant reduction only of TNF-a and fibrinogen. |
| 2899 | 21894160 | Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4. |
| 2900 | 21900603 | In isolated macrophages, ERα was necessary for repression of inflammation, maintenance of oxidative metabolism, IL-4-mediated induction of alternative activation, full phagocytic capacity in response to LPS, and oxidized LDL-induced expression of ApoE and Abca1. |
| 2901 | 21984919 | Compared with the healthy control mice, diabetic mice had significantly fewer c-kit+ stem cells, and these cells had a lower potency of endothelial differentiation; however, the production of the angiogenic growth factor VEGF did not differ between groups. |
| 2902 | 21984919 | A pathway-focused array showed that the c-kit+ stem cells from diabetic mice had up-regulated expression levels of many inflammatory factors, including Tlr4, Cxcl9, Il9, Tgfb1, Il4, and Tnfsf5, but no obvious change in the expression levels of cell cycle molecules. |
| 2903 | 21984919 | Interestingly, diabetes-related alterations of the extracellular matrix and adhesion molecules were varied; Pecam, Mmp10, Lamc1, Itgb7, Mmp9, and Timp4 were up-regulated, but Col11a1, Fn1, Admts2, and Itgav were down-regulated. |
| 2904 | 22043003 | To test this, we treated hyperglycemic NOD mice with F(ab')(2) fragments of anti-CD3 mAb with or without IL-1 receptor antagonist (IL-1RA), or anti-IL-1β mAb. |
| 2905 | 22043003 | Combination-treated mice had increased IL-5, IL-4, and interferon (IFN)-γ levels in circulation. |
| 2906 | 22043003 | After 1 month, there were increased concentrations of IgG1 isotype antibodies and reduced intrapancreatic expression of IFN-γ, IL-6, and IL-17 despite normal splenocyte cytokine secretion. |
| 2907 | 22076555 | Cationic nanomicelles for delivery of plasmids encoding interleukin-4 and interleukin-10 for prevention of autoimmune diabetes in mice. |
| 2908 | 22089495 | Our results demonstrate that a single treatment with dsAAV8 vectors expressing IL-4 in combination with glucagon-like peptide-1 or hepatocyte growth factor/NK1 under the regulation of the insulin promoter enhanced β-cell proliferation and survival in vivo, significantly delaying diabetes progression in NOD mice, and reversing disease in ∼10% of treated NOD mice. |
| 2909 | 22156208 | Here we report that macrophages lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to IL-4-induced alternative activation and, furthermore, are hyperresponsive to IL-4 stimulation. |
| 2910 | 22156208 | Throughout the macrophage genome, HDAC3 deacetylates histone tails at regulatory regions, leading to repression of many IL-4-regulated genes characteristic of alternative activation. |
| 2911 | 22156208 | Here we report that macrophages lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to IL-4-induced alternative activation and, furthermore, are hyperresponsive to IL-4 stimulation. |
| 2912 | 22156208 | Throughout the macrophage genome, HDAC3 deacetylates histone tails at regulatory regions, leading to repression of many IL-4-regulated genes characteristic of alternative activation. |
| 2913 | 22174447 | We tested these hypotheses by investigating whether infection with the filarial nematode Litomosoides sigmodontis prevents diabetes onset in IL-4-deficient NOD mice and whether depletion or absence of regulatory T cells, IL-10, or TGF-β alters helminth-mediated protection. |
| 2914 | 22174447 | Infections in immunocompetent and IL-4-deficient NOD mice were accompanied by increases in CD4(+)CD25(+)Foxp3(+) regulatory T cell frequencies and numbers, respectively, and helminth infection increased the proliferation of CD4(+)Foxp3(+) cells. |
| 2915 | 22174447 | We tested these hypotheses by investigating whether infection with the filarial nematode Litomosoides sigmodontis prevents diabetes onset in IL-4-deficient NOD mice and whether depletion or absence of regulatory T cells, IL-10, or TGF-β alters helminth-mediated protection. |
| 2916 | 22174447 | Infections in immunocompetent and IL-4-deficient NOD mice were accompanied by increases in CD4(+)CD25(+)Foxp3(+) regulatory T cell frequencies and numbers, respectively, and helminth infection increased the proliferation of CD4(+)Foxp3(+) cells. |
| 2917 | 22178606 | We report here that high glucose (HG) treatment stimulated astrocytic morphological alteration coupled with changes in glial fibrillary acidic protein (GFAP) and vimentin expression. |
| 2918 | 22178606 | Additionally, HG upregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-4 (IL-4), and vascular endothelial growth factor (VEGF); however, its effects on transforming growth factor-β (TGF-β) expression were not evident. |
| 2919 | 22178606 | HG treatment induced increased production of reactive oxygen species (ROS) as well as activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator transcription 3 (STAT 3). |
| 2920 | 22178606 | HG-induced expression of TNF-α, IL-6, IL-1β, IL-4, and VEGF was blocked by ROS scavenger and inhibitors specific for NF-κB and STAT 3, respectively. |
| 2921 | 22178606 | We report here that high glucose (HG) treatment stimulated astrocytic morphological alteration coupled with changes in glial fibrillary acidic protein (GFAP) and vimentin expression. |
| 2922 | 22178606 | Additionally, HG upregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-4 (IL-4), and vascular endothelial growth factor (VEGF); however, its effects on transforming growth factor-β (TGF-β) expression were not evident. |
| 2923 | 22178606 | HG treatment induced increased production of reactive oxygen species (ROS) as well as activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator transcription 3 (STAT 3). |
| 2924 | 22178606 | HG-induced expression of TNF-α, IL-6, IL-1β, IL-4, and VEGF was blocked by ROS scavenger and inhibitors specific for NF-κB and STAT 3, respectively. |
| 2925 | 22586579 | The 3-phosphoinositide-dependent protein kinase 1 (Pdk1)/forkhead transcription factor (Foxo1) pathway is important in regulating glucose and energy homeostasis, but little is known about this pathway in adipose tissue macrophages (ATMs). |
| 2926 | 22586579 | To investigate this, we generated transgenic mice that carried macrophage/granulocyte-specific mutations, including a Pdk1 knockout (LysMPdk1(-/-)), a Pdk1 knockout with transactivation-defective Foxo1 (Δ256LysMPdk1(-/-)), a constitutively active nuclear (CN) Foxo1 (CNFoxo1(LysM)), or a transactivation-defective Foxo1 (Δ256Foxo1(LysM)). |
| 2927 | 22586579 | CNFoxo1(LysM) promoted transcription of the C-C motif chemokine receptor 2 (Ccr2) in ATMs and increased M1 macrophages in adipose tissue. |
| 2928 | 22586579 | Pdk1 deletion or Foxo1 activation in bone marrow-derived macrophages abolished insulin and interleukin-4 induction of genes involved in alternative macrophage activation. |
| 2929 | 22586579 | Thus, Pdk1 regulated macrophage infiltration by inhibiting Foxo1-induced Ccr2 expression. |
| 2930 | 22586579 | This shows that the macrophage Pdk1/Foxo1 pathway is important in regulating insulin sensitivity in vivo. |
| 2931 | 22728763 | Targeting Janus tyrosine kinase 3 (JAK3) with an inhibitor induces secretion of TGF-β by CD4+ T cells. |
| 2932 | 22728763 | Here, we show that the JAK3 inhibitor 4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) suppresses proliferation of short-term cultured NOD CD4(+) T cells through induction of apoptosis, while promoting survival of a particular population of long-term cultured cells. |
| 2933 | 22728763 | It was found that the surviving cells were not of the CD4(+)CD25(+)FoxP3(+) phenotype. |
| 2934 | 22728763 | They secreted decreased amounts of IL-10, IL-4 and interferon (IFN)-γ compared to the cells not exposed to the optimal concentrations of JAK3 inhibitor. |
| 2935 | 22728763 | In vivo treatment of prediabetic NOD mice with WHI-P131 did not affect the frequency and number of splenic and pancreatic lymph node CD4(+)FoxP3(+) Tregs, while generating an elevated numbers of CD4(+)FoxP3(-) TGF-β-secreting T cells. |
| 2936 | 22728763 | In conclusion, our data suggest an induction of TGF-β-secreting CD4(+) T cells as the underlying mechanism for antidiabetogenic effects obtained by the treatment with a JAK3 inhibitor. |
| 2937 | 22745325 | We used a panel of cytokines and other stimuli to discern the most effective regimen for in vitro induction of immunosuppressive macrophages (M2r) and determined interleukin (IL)-4/IL-10/transforming growth factor-β (TGF-β) to be optimal. |
| 2938 | 22745325 | M2r cells expressed programmed cell death 1 ligand-2, fragment crystallizable region γ receptor IIb, IL-10, and TGF-β, had a potent deactivating effect on proinflammatory lipopolysaccharide/interferon-γ-stimulated macrophages, and significantly suppressed T-cell proliferation. |
| 2939 | 22888041 | The concentrations of IL-4 and IL-8 were significantly increased in allogeneic serum, which induced a pro-inflammatory environment, including the release of IL-4, IL-6, IL-8 and MCP-1 into the conditioned media of cell cultures. |
| 2940 | 22906888 | IL-1β, IL-18, IL-12, IL-10 and IL-4 were significantly higher among the youngest children and males had significantly lower levels of IL-10 and IL-12 but higher levels of TNF-α. |
| 2941 | 22936933 | Studies employing mice lacking a functional p110δ protein, as well as the use of highly-selective chemical inhibitors of p110δ, have revealed that signaling via p110δ-containing PI3K complexes (PI3Kδ) is critical for B-cell survival, migration, and activation, functioning downstream of key receptors on B cells including the B-cell antigen receptor, chemokine receptors, pro-survival receptors such as BAFF-R and the IL-4 receptor, and co-stimulatory receptors such as CD40 and Toll-like receptors (TLRs). |
| 2942 | 23149823 | These were accompanied by overexpression of negative regulators of NFκB, TLR, and other proinflammatory pathways, e.g., A20, SOCS1, IRAK-M, IκBα, Triad3A, Tollip, SIGIRR, and ST2L. |
| 2943 | 23149823 | Anti-inflammatory and immunomodulatory molecules, e.g., IL-10, IL-4, and TSLP that favor TH2 responses were strongly induced. |
| 2944 | 23213311 | EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE(2), as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. |
| 2945 | 23213311 | Furthermore, activation of the nuclear transcription factor, NF-κB, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. |
| 2946 | 23349499 | Cereal-SPF rats displayed increased gut CD3(+) and CD8α(+) lymphocytes, ratio of Ifng to Il4 mRNA, and Lck expression, indicating T-cell activation. |
| 2947 | 23349499 | The cathelicidin antimicrobial peptide (Camp) gene was upregulated in the jejunum of HC diet-protected rats, and CAMP(+) cells colocalized with CD163. |
| 2948 | 23405091 | In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. |
| 2949 | 23405091 | Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production. |
| 2950 | 23405091 | In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. |
| 2951 | 23405091 | Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production. |
| 2952 | 23421092 | Trials of recombinant interleukin production in plants relate almost exclusively to tobacco, where through the transformation of the nuclear genome (agroinfection) monomeric (IL-2, IL-4, IL-13, IL-18), homodimeric (IL-10) and single-chain heterodimeric (IL-12) interleukins have been obtained. |
| 2953 | 23428339 | Cultures from case subjects produced higher levels of IL-10, IL-13, IL-4, IL-5, IL-17, and IL-6, when stimulated with mitogen compared with control subjects. |
| 2954 | 23554983 | Xenogeneic immune response to encapsulated FP ICCs was associated with enhanced intragraft mRNA expression of porcine antigens MIP-1α, IL-8, HMGB1 and HSP90 seen within the first two weeks post-transplantation. |
| 2955 | 23554983 | The anti-inflammatory cytokines detected were IL-5 and IL-4 with levels peaking at days 1 and 7, respectively. |
| 2956 | 23600826 | Concentrations of proinflammatory cytokines interleukin (IL)-1β, IL-2, IL-12(p70), IL-18, IFN-γ, of regulatory cytokines IL-4, IL-10, IL-17 and chemokine CCL2 (MCP-1) were measured by multiplex-bead technology from supernatants. |
| 2957 | 23600826 | Co-incubation of fatty acids with uric acid resulted in a significant reduction of IL-10, IL-12(p70), IFN-γ and CCL2 (MCP-1) concentrations in supernatants compared to incubation with uric acid alone (P < 0·0001). |
| 2958 | 23600826 | Similarly, co-incubation of fatty acids with glucose diminished secretion of IL-10, IFN-γ and CCL2 (monocyte chemotactic protein-1), while IL-8 was up-regulated (P < 0·001). |
| 2959 | 23630352 | OX40L/Jagged1 cosignaling by GM-CSF-induced bone marrow-derived dendritic cells is required for the expansion of functional regulatory T cells. |
| 2960 | 23630352 | Concurrent signaling induced by OX40L and Jagged1 via OX40 and Notch3 receptors expressed on Tregs was essential for the Treg expansion with sustained FoxP3 expression. |
| 2961 | 23630352 | Adoptive transfer of only OX40L(+)Jagged1(+) BMDCs led to Treg expansion, increased production of IL-4 and IL-10, and suppression of EAT in the recipient mice. |
| 2962 | 23651394 | Increases in serum and urine galactose and urine galactitol were observed in the second month of life in formula-fed infants, along with higher levels of TNFα, IFN-γ, IL-1β, IL-4, and other cytokines and growth factors at week 4. |
| 2963 | 23664771 | We previously reported that IL-1 Trap (a hybrid molecule consisting of the extracellular domain of IL-1 receptor accessory protein and IL-1 receptor type 1 arranged inline and fused to the Fc-portion of IgG1) can protect rat pancreatic islets in vitro against noxious effects induced by IL-1β. |
| 2964 | 23664771 | The treatments were maintained until ROD (i.e. a blood glucose value ⩾11.1mM for 2 consecutive days) or until 5days after transplantation. 3 out of 11 mice treated with IL-1 Trap showed a significantly increased graft survival compared to all other mice, and analysis of relative cytokine mRNA levels in isolated spleen cells showed elevated IL-4 mRNA levels, but no differences in FoxP3 or iNOS staining of grafts, from mice treated with IL-1 Trap, at both endpoints, compared to both control groups. |
| 2965 | 23739939 | We then review research on R/S, cardiovascular functions (CV reactivity, heart rate variability, etc.), and inflammatory markers (IL-6, IFN-γ, CRP, fibrinogen, IL-4, IL-10). |
| 2966 | 23769592 | Plasma concentrations of interleukin (IL)-5, IL-6, IL-7, tumor necrosis factor-α (TNF-α), and granulocyte-monocyte colony-stimulating factor (GM-CSF) were significantly higher in the prediabetic group, as compared to the control group (all p<0.05). |
| 2967 | 23769592 | Plasma concentrations of all the other cytokines, interferon-γ (IFN-γ), IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70 and IL-13, seemed to be elevated in the prediabetic group, but failed to reach statistical significances. |
| 2968 | 23769592 | Upon merging both groups, HbA1c was found to be positively correlated with IFN-γ, IL-1β, IL-2, IL-5, IL-7, IL-8, TNF-α and GM-CSF. |
| 2969 | 23778688 | Ventricular hemodynamic parameters were recorded; fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were determined using an automatic biochemistry analyzer; plasma interleukin (IL)-1, IL-4 and cardiac 4-hydroxynon-2-enal (4-HNE) levels were determined using enzyme-linked immunosorbent assay (ELISA), and cardiac ALDH2 activity was measured. |
| 2970 | 23778688 | The mRNA expression levels of Bax and Bcl-2 of the left anterior myocardium were detected by reverse transcriptase‑polymerase chain reaction (RT-PCR). |
| 2971 | 23778688 | The left ventricular developed pressure (LVDP), heart rate (HR) and rate-pressure product (RPP) were decreased, plasma IL-1 levels were increased, while IL-4 levels were decreased in the DM groups compared to the control group. |
| 2972 | 23778688 | Bax mRNA levels were increased, Bcl-2 mRNA levels were decreased, and Bcl-2/Bax mRNA ratios were decreased in the DM groups compared to the control group. |
| 2973 | 23778688 | Moreover, LVDP, HR, RPP, IL-4, ALDH2 activity and Bcl-2/Bax mRNA ratios were further reduced, while 4-HNE and IL-1 levels were increased with the progression of diabetes. |
| 2974 | 23778688 | Ventricular hemodynamic parameters were recorded; fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were determined using an automatic biochemistry analyzer; plasma interleukin (IL)-1, IL-4 and cardiac 4-hydroxynon-2-enal (4-HNE) levels were determined using enzyme-linked immunosorbent assay (ELISA), and cardiac ALDH2 activity was measured. |
| 2975 | 23778688 | The mRNA expression levels of Bax and Bcl-2 of the left anterior myocardium were detected by reverse transcriptase‑polymerase chain reaction (RT-PCR). |
| 2976 | 23778688 | The left ventricular developed pressure (LVDP), heart rate (HR) and rate-pressure product (RPP) were decreased, plasma IL-1 levels were increased, while IL-4 levels were decreased in the DM groups compared to the control group. |
| 2977 | 23778688 | Bax mRNA levels were increased, Bcl-2 mRNA levels were decreased, and Bcl-2/Bax mRNA ratios were decreased in the DM groups compared to the control group. |
| 2978 | 23778688 | Moreover, LVDP, HR, RPP, IL-4, ALDH2 activity and Bcl-2/Bax mRNA ratios were further reduced, while 4-HNE and IL-1 levels were increased with the progression of diabetes. |
| 2979 | 23778688 | Ventricular hemodynamic parameters were recorded; fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were determined using an automatic biochemistry analyzer; plasma interleukin (IL)-1, IL-4 and cardiac 4-hydroxynon-2-enal (4-HNE) levels were determined using enzyme-linked immunosorbent assay (ELISA), and cardiac ALDH2 activity was measured. |
| 2980 | 23778688 | The mRNA expression levels of Bax and Bcl-2 of the left anterior myocardium were detected by reverse transcriptase‑polymerase chain reaction (RT-PCR). |
| 2981 | 23778688 | The left ventricular developed pressure (LVDP), heart rate (HR) and rate-pressure product (RPP) were decreased, plasma IL-1 levels were increased, while IL-4 levels were decreased in the DM groups compared to the control group. |
| 2982 | 23778688 | Bax mRNA levels were increased, Bcl-2 mRNA levels were decreased, and Bcl-2/Bax mRNA ratios were decreased in the DM groups compared to the control group. |
| 2983 | 23778688 | Moreover, LVDP, HR, RPP, IL-4, ALDH2 activity and Bcl-2/Bax mRNA ratios were further reduced, while 4-HNE and IL-1 levels were increased with the progression of diabetes. |
| 2984 | 23803704 | No significant changes were noted in interferon-γ, interleukin-4 (IL-4), or IL-10 production in CD4 T cells. |
| 2985 | 23837227 | The inflammatory disturbances in the interior of the eye chamber are characterised primarly by the changes of the IFN-gamma, IgG and IL-4 concentration and appearance of the oligoclonal IgG. |
| 2986 | 23934388 | Interleukin (IL)-7 is one of the IL-2 family cytokines comprised of IL-2, IL-4, IL-7, IL-9, IL-15, as well as IL-21. |
| 2987 | 23964268 | In the context of insulin action, M2 macrophages sustain insulin sensitivity by secreting IL-4 and IL-10, while M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines, such as TNFα. |
| 2988 | 23964268 | It has been demonstrated that, in a lean state, TH2 cells, Treg cells, natural killer T cells, or eosinophils contribute to the M2 activation of macrophages by secreting IL-4 or IL-10. |
| 2989 | 23964268 | In the context of insulin action, M2 macrophages sustain insulin sensitivity by secreting IL-4 and IL-10, while M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines, such as TNFα. |
| 2990 | 23964268 | It has been demonstrated that, in a lean state, TH2 cells, Treg cells, natural killer T cells, or eosinophils contribute to the M2 activation of macrophages by secreting IL-4 or IL-10. |
| 2991 | 24005626 | Several mechanisms including IL-4 and IL-10 production by NKT cells and the accumulation of tolerogenic dendritic cells are critical for the dampening of pathogenic anti-islet T cell responses by NKT cells. |