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Gene Information
Gene symbol: CD4
Gene name: CD4 molecule
HGNC ID: 1678
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1343880 | From 14 days after vaccination, BAL cultures contained infiltrating lymphocytes which produced abundant quantities of IFN-g and IL-3. |
| 2 | 1343880 | Challenge of vaccinated mice resulted in a second influx of IFN-g and IL-3--producing cells, earlier than after vaccination or in the appropriate controls. |
| 3 | 1343880 | Ablation studies revealed that CD4+ T cells were the source of IFN-g. |
| 4 | 1371640 | CD4/CD8 ratio and percentage CD4 were normal in peripheral blood. |
| 5 | 1371640 | Analysis of the pleural effusion revealed an increased CD4/CD8 ratio because of an increased percentage of CD4+CD29+ helper memory T cells, lack of expression of the resting B-cell marker CD21, immune complex deposition and complement consumption, increased relative levels of ANA, abnormally high levels of IL-6 and soluble IL-2R, and detectable levels of IL-1b, IFN-g and TNF-a. |
| 6 | 1371640 | CD4/CD8 ratio and percentage CD4 were normal in peripheral blood. |
| 7 | 1371640 | Analysis of the pleural effusion revealed an increased CD4/CD8 ratio because of an increased percentage of CD4+CD29+ helper memory T cells, lack of expression of the resting B-cell marker CD21, immune complex deposition and complement consumption, increased relative levels of ANA, abnormally high levels of IL-6 and soluble IL-2R, and detectable levels of IL-1b, IFN-g and TNF-a. |
| 8 | 1399092 | Serial measurements were made during each treatment of interleukin-1 beta (II-1 beta), TNF, soluble IL-2 receptor (sII-2r), soluble CD4 (sCD4), soluble CD8 (sCD8), interferon gamma (IFNg) and neopterin. |
| 9 | 1399092 | In contrast to the known increase of IL-1 beta, IL-2r and TNF with cuprophane membranes, none of the modern high-flux dialyzers stimulated the production of these factors. |
| 10 | 2219270 | In contrast, suppression in the recipient spleens was donor-specific; both CD4 and CD8 cells prolonged test graft survival. |
| 11 | 2219270 | Immunohistological evaluation of renal allografts revealed that therapy with ART-18 or low-dose CsA alone failed to deplete IL-2R+ cells and prevent production of IL-2, IFN-g, and TNF. |
| 12 | 7663570 | Lymph nodes containing microscopic tumor and shed mucin exhibited approximately 40-fold expansion in short-term (< 21 days) cultures with either IL-2 or IL-1 plus IL-2; the combination of IL-2/anti-CD3 monoclonal antibody (mAb) resulted in significantly higher expansion. |
| 13 | 7663570 | Cultures generated with IL-2 alone favored the expansion of CD8+ and CD56+ cells, whereas addition of IL-1 or anti-CD3 mAb to IL-2 promoted outgrowth of CD4+ T-cells. |
| 14 | 7663570 | However, CD4+ cells expanded in IL-2/anti-CD3 retained the ability to proliferate in response to TAG-72 mucin-expressing autologous tumor as well as bovine submaxillary mucin (BSM) a soluble TAG-72+ mucin. |
| 15 | 7663570 | In addition, CD4+ cells expressed mRNA for IL-2, IL-4, tumor necrosis factor-beta and IFNg, and retained the ability to secrete IL-2 after expansion. |
| 16 | 7663570 | Lymph nodes containing microscopic tumor and shed mucin exhibited approximately 40-fold expansion in short-term (< 21 days) cultures with either IL-2 or IL-1 plus IL-2; the combination of IL-2/anti-CD3 monoclonal antibody (mAb) resulted in significantly higher expansion. |
| 17 | 7663570 | Cultures generated with IL-2 alone favored the expansion of CD8+ and CD56+ cells, whereas addition of IL-1 or anti-CD3 mAb to IL-2 promoted outgrowth of CD4+ T-cells. |
| 18 | 7663570 | However, CD4+ cells expanded in IL-2/anti-CD3 retained the ability to proliferate in response to TAG-72 mucin-expressing autologous tumor as well as bovine submaxillary mucin (BSM) a soluble TAG-72+ mucin. |
| 19 | 7663570 | In addition, CD4+ cells expressed mRNA for IL-2, IL-4, tumor necrosis factor-beta and IFNg, and retained the ability to secrete IL-2 after expansion. |
| 20 | 7663570 | Lymph nodes containing microscopic tumor and shed mucin exhibited approximately 40-fold expansion in short-term (< 21 days) cultures with either IL-2 or IL-1 plus IL-2; the combination of IL-2/anti-CD3 monoclonal antibody (mAb) resulted in significantly higher expansion. |
| 21 | 7663570 | Cultures generated with IL-2 alone favored the expansion of CD8+ and CD56+ cells, whereas addition of IL-1 or anti-CD3 mAb to IL-2 promoted outgrowth of CD4+ T-cells. |
| 22 | 7663570 | However, CD4+ cells expanded in IL-2/anti-CD3 retained the ability to proliferate in response to TAG-72 mucin-expressing autologous tumor as well as bovine submaxillary mucin (BSM) a soluble TAG-72+ mucin. |
| 23 | 7663570 | In addition, CD4+ cells expressed mRNA for IL-2, IL-4, tumor necrosis factor-beta and IFNg, and retained the ability to secrete IL-2 after expansion. |
| 24 | 8105441 | All seven clones/lines were CD4+, CD8- and expressed high levels of CD44 and CD45RB surface markers. |
| 25 | 8972688 | Comparison of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and interferon-gamma. |
| 26 | 8972688 | Oxidative burst response upon stimulation with N-formyl-methionyl-leucyl-phenylalanine was assessed in neutrophils after priming with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-g), and in monocytes after priming with GM-CSF and IFN-g. |
| 27 | 8972688 | In contrast, following priming with IFN-g, GM-CSF or medium (but not G-CSF) the neutrophils in HIV patients with CD4 counts > 200 x 10(9)/L exhibited a significantly higher chemiluminescence response than was seen in healthy age-matched controls, whereas the response in patients with lower CD4 counts was not different from controls. |
| 28 | 8972688 | At comparable concentrations, GM-CSF induced a significantly higher priming than G-CSF and IFN-g. |
| 29 | 8972688 | A significant positive correlation between CD4 counts and priming activity of GM-CSF and IFN-g on neutrophils was observed. |
| 30 | 8972688 | Comparison of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and interferon-gamma. |
| 31 | 8972688 | Oxidative burst response upon stimulation with N-formyl-methionyl-leucyl-phenylalanine was assessed in neutrophils after priming with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-g), and in monocytes after priming with GM-CSF and IFN-g. |
| 32 | 8972688 | In contrast, following priming with IFN-g, GM-CSF or medium (but not G-CSF) the neutrophils in HIV patients with CD4 counts > 200 x 10(9)/L exhibited a significantly higher chemiluminescence response than was seen in healthy age-matched controls, whereas the response in patients with lower CD4 counts was not different from controls. |
| 33 | 8972688 | At comparable concentrations, GM-CSF induced a significantly higher priming than G-CSF and IFN-g. |
| 34 | 8972688 | A significant positive correlation between CD4 counts and priming activity of GM-CSF and IFN-g on neutrophils was observed. |
| 35 | 9116875 | In an attempt to understand the mechanism behind these differences we examined age related differences in the phenotype profiles of MNC in parallel with the in vitro production of interleukin IL-6, tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFNg) in neonates, children and adults. |
| 36 | 9116875 | In cultures without added polyclonal activators IL-6 and TNF alpha levels in children were 3-6 times higher than those of umbilical cords and adults. |
| 37 | 9116875 | Flow cytometry analysis of the phenotypic distribution of MNC revealed age related differences in the expression of CD3, CD4, CD8, CD14, CD19, CD45RA, CD45R0, CD2, LFA-1, ICAM-1 and LFA-3. |
| 38 | 9116875 | The TNF alpha levels in suboptimally stimulated cultures correlated negatively with the expression of LFA-3 and positively with CD45RA, while IFNg correlated positively with CD2, LFA-1, CD45R0 and CD8. |
| 39 | 9116875 | In conclusion, the study provides evidence of age related differences in the production of TNF alpha, IL-6 and IFNg among neonates, children and adults. |
| 40 | 9656442 | Influence of IL-12 on interferon-gamma production by bovine leucocyte subsets in response to bovine respiratory syncytial virus. |
| 41 | 9656442 | The cytokine IL-12 is a key molecule in the regulation of CD4+ T cell development and specifically potentiates the development of T helper 1 responses in mouse and man. |
| 42 | 9656442 | Here the 2A was flanked by sequences encoding the p35 and p40 polypeptides of the heterodimeric cytokine to mediate their cleavage. |
| 43 | 9656442 | The presence of IL-12 markedly influenced the level of IFNg secreted by these cells, and although IL-12 induced IFNg production in the absence of antigenic stimulation, IFNg production was accelerated and augmented in response to IL-12 and antigen. |
| 44 | 9656442 | Analysis of the T cell subsets by flow cytometry showed that CD4+ T cells comprised the largest contributors to IFNg production. |
| 45 | 9656442 | Influence of IL-12 on interferon-gamma production by bovine leucocyte subsets in response to bovine respiratory syncytial virus. |
| 46 | 9656442 | The cytokine IL-12 is a key molecule in the regulation of CD4+ T cell development and specifically potentiates the development of T helper 1 responses in mouse and man. |
| 47 | 9656442 | Here the 2A was flanked by sequences encoding the p35 and p40 polypeptides of the heterodimeric cytokine to mediate their cleavage. |
| 48 | 9656442 | The presence of IL-12 markedly influenced the level of IFNg secreted by these cells, and although IL-12 induced IFNg production in the absence of antigenic stimulation, IFNg production was accelerated and augmented in response to IL-12 and antigen. |
| 49 | 9656442 | Analysis of the T cell subsets by flow cytometry showed that CD4+ T cells comprised the largest contributors to IFNg production. |
| 50 | 11217546 | This phase corresponds to early release of so-called inflammatory cytokines (IL1, IL6, IL8). |
| 51 | 11217546 | The second phase consists of recognition of bacterial antigens by helper CD4 lymphocytes, which mainly release IL2 and IFNg (Th1 response). |
| 52 | 11606479 | Although most investigators focus on the role of CD4+ T cells in demyelinating disease, these studies are the first to demonstrate a clear contribution of antiviral CD8+ T cells in neurological injury in a chronic-progressive model of multiple sclerosis. |
| 53 | 12719555 | Interestingly, Tmevpg1 is down regulated after in vitro stimulation of murine CD4(+) or CD8(+) splenocytes, whereas Ifng is up regulated. |
| 54 | 12719555 | Similar patterns of expression of TMEVPG1 and IFNG were observed in human NK cells and CD4(+) and CD8(+) T lymphocytes. |
| 55 | 12719555 | Interestingly, Tmevpg1 is down regulated after in vitro stimulation of murine CD4(+) or CD8(+) splenocytes, whereas Ifng is up regulated. |
| 56 | 12719555 | Similar patterns of expression of TMEVPG1 and IFNG were observed in human NK cells and CD4(+) and CD8(+) T lymphocytes. |
| 57 | 12854077 | A tumor necrosis factor-alpha-inducible promoter variant of interferon-gamma accelerates CD4+ T cell depletion in human immunodeficiency virus-1-infected individuals. |
| 58 | 12854077 | A polymorphism, -179G/T, in the promoter of the interferon (IFN)-gamma gene (IFNG) confers differential tumor necrosis factor-alpha (TNF-alpha) inducibility to the IFNG promoter. |
| 59 | 12854077 | In 298 African American human immunodeficiency virus (HIV)-1 seroconverters, the IFNG -179G/T genotype was associated with accelerated progression to CD4 <200 and AIDS-1993, a finding suggesting that IFNG -179T is a risk factor for AIDS progression, as measured by CD4 cell count. |
| 60 | 12854077 | It is possible that increased IFN-gamma production induced by TNF-alpha when -179T is present causes CD4 cell depletion by apoptosis. |
| 61 | 12854077 | A tumor necrosis factor-alpha-inducible promoter variant of interferon-gamma accelerates CD4+ T cell depletion in human immunodeficiency virus-1-infected individuals. |
| 62 | 12854077 | A polymorphism, -179G/T, in the promoter of the interferon (IFN)-gamma gene (IFNG) confers differential tumor necrosis factor-alpha (TNF-alpha) inducibility to the IFNG promoter. |
| 63 | 12854077 | In 298 African American human immunodeficiency virus (HIV)-1 seroconverters, the IFNG -179G/T genotype was associated with accelerated progression to CD4 <200 and AIDS-1993, a finding suggesting that IFNG -179T is a risk factor for AIDS progression, as measured by CD4 cell count. |
| 64 | 12854077 | It is possible that increased IFN-gamma production induced by TNF-alpha when -179T is present causes CD4 cell depletion by apoptosis. |
| 65 | 12854077 | A tumor necrosis factor-alpha-inducible promoter variant of interferon-gamma accelerates CD4+ T cell depletion in human immunodeficiency virus-1-infected individuals. |
| 66 | 12854077 | A polymorphism, -179G/T, in the promoter of the interferon (IFN)-gamma gene (IFNG) confers differential tumor necrosis factor-alpha (TNF-alpha) inducibility to the IFNG promoter. |
| 67 | 12854077 | In 298 African American human immunodeficiency virus (HIV)-1 seroconverters, the IFNG -179G/T genotype was associated with accelerated progression to CD4 <200 and AIDS-1993, a finding suggesting that IFNG -179T is a risk factor for AIDS progression, as measured by CD4 cell count. |
| 68 | 12854077 | It is possible that increased IFN-gamma production induced by TNF-alpha when -179T is present causes CD4 cell depletion by apoptosis. |
| 69 | 12937840 | Progressive ascitic growth of a spontaneous transplantable T-cell lymphoma, designated as Dalton's lymphoma (DL), in a murine host has been shown to be associated with an involution of thymus accompanied by a massive depletion of the cortical region and an alteration in the distribution of thymocytes by a decrease of CD4+CD8+, CD4+CD8- and CD4-CD8+ phenotypes caused by an enhanced induction of apoptosis in thymocytes. |
| 70 | 14565821 | The number of spleen cells, the percentages of B and T cells, and the distribution of T-cell subpopulations (CD4 and CD8) were not altered by the exposure. |
| 71 | 14628087 | Both CD8+ and CD4+ T cells with specific activity against tumor antigens are needed for an efficient antitumor immune response. |
| 72 | 14628087 | DCs were obtained from peripheral blood mononuclear cells (PBMC) in the presence of IL-4 and GM-CSF. |
| 73 | 14628087 | Nonadherent peripheral blood mononuclear cells were cultured in the presence of Il-2 and IL-7. |
| 74 | 14691261 | Here, we analyze chromatin conformation of the 24-kb region of the Ifng gene during CD4(+) T helper (Th) cell differentiation. |
| 75 | 15304658 | When linked to the murine Ifng gene (-3.4 to +5.6 kb) and transiently transfected into EL-4 cells, these elements clearly enhanced IFN-gamma expression in response to ionomycin and phorbol 12-myristate 13-acetate and weakly enhanced expression in response to T-bet. |
| 76 | 15304658 | A DNase I hypersensitive site and extragenic transcripts at IFNgCNS2 correlated positively with the capacity of primary T cell subsets to produce IFN-gamma. |
| 77 | 15304658 | Transcriptionally favorable histone modifications in the Ifng promoter, intronic regions, IFNgCNS2, and, although less pronounced, IFNgCNS1 increased as naïve T cells differentiated into IFN-gamma-producing effector CD8+ and T helper (TH) 1 T cells, but not into TH2 T cells. |
| 78 | 15304658 | Like IFN-gamma expression, these histone modifications were T-bet-dependent in CD4+ cells, but not CD8+ T cells. |
| 79 | 15597669 | The cytokine response detected in ABPA patients is of a CD4+ Th2 type as evidenced by the production of IL-4, IL-5, and very little or no IFN-g on stimulation of T-lymphocytes with Aspergillus antigens. |
| 80 | 15659263 | The role of distinct CD4+ T-cell populations in regulating the nature and strength of immune responses is well documented, and has in the past principally focused on the mutual antagonism between Th1 and Th2 cells, which secrete interferon (IFN)-gamma and interleukin (IL)-4, respectively. |
| 81 | 15659263 | However, the recent identification of T cells that secrete high levels of IL-10 and/or transforming growth factor-b, but not IFN-g or IL-4, called regulatory T (Tr) cells has prompted a paradigm shift in our understanding of the regulation of immune responses following infection. |
| 82 | 16520391 | T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. |
| 83 | 16520391 | T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3. |
| 84 | 16520391 | Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling. |
| 85 | 16520391 | In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity. |
| 86 | 16520391 | In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed. |
| 87 | 16520391 | Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels. |
| 88 | 16520391 | These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet. |
| 89 | 16520391 | Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene. |
| 90 | 16563877 | CD8+ CTL (cytotoxic T-lymphocyte)-derived IFN-g may be especially important both for cells lacking MHC class II molecules, e.g. in the lung and for macrophages where mycobacteria can evade recognition during chronic infection by sequestering their antigens away from sensitized CD4+ T cells. |
| 91 | 17093503 | Here, we analyzed nuclear matrix attachment regions (MARs) in the Ifng gene by DNA array technique in unactivated and activated CD4+ Th cells. |
| 92 | 17093503 | The data suggest that such structural dynamics provide the means for transcriptional regulation of the Ifng gene in the course of activation and differentiation of CD4+Th cells. |
| 93 | 17093503 | Here, we analyzed nuclear matrix attachment regions (MARs) in the Ifng gene by DNA array technique in unactivated and activated CD4+ Th cells. |
| 94 | 17093503 | The data suggest that such structural dynamics provide the means for transcriptional regulation of the Ifng gene in the course of activation and differentiation of CD4+Th cells. |
| 95 | 17583733 | Recruitment of the RNA polymerase II transcription complex to the promoter of the Ifng gene has been studied by chromatin immunoprecipitation (ChIP) in activated functionally different CD4+ T helper (Th) cell subsets. |
| 96 | 17675500 | IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes. |
| 97 | 17675500 | Memory Th cells secreting IL-10 or IFN-gamma were directly isolated ex vivo from peripheral blood of healthy volunteers, and the DNA methylation status of IL10 and IFNG was assessed. |
| 98 | 17675500 | Our data indicate that IL10 does not become epigenetically marked in human memory Th cells unlike effector cytokine genes such as IFNG. |
| 99 | 17675500 | The exclusion of IL-10, but not effector cytokines, from the functional memory of human CD4(+) T lymphocytes ex vivo may reflect the need for appropriate regulation of IL-10 secretion, due to its potent immunoregulatory potential. |
| 100 | 17675500 | IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes. |
| 101 | 17675500 | Memory Th cells secreting IL-10 or IFN-gamma were directly isolated ex vivo from peripheral blood of healthy volunteers, and the DNA methylation status of IL10 and IFNG was assessed. |
| 102 | 17675500 | Our data indicate that IL10 does not become epigenetically marked in human memory Th cells unlike effector cytokine genes such as IFNG. |
| 103 | 17675500 | The exclusion of IL-10, but not effector cytokines, from the functional memory of human CD4(+) T lymphocytes ex vivo may reflect the need for appropriate regulation of IL-10 secretion, due to its potent immunoregulatory potential. |
| 104 | 17715431 | The proportions of CD4(+) and CD8(+) cells were unchanged, but the number of gamma delta T cells was increased by coculture with luteal cells. |
| 105 | 17715431 | The concentrations of interferon-gamma (IFNG) and interleukin 10 (IL10) were increased in luteal cell-T cell cocultures, whereas IL4 was undetectable, and IL12 was barely detectable in culture medium. |
| 106 | 17981204 | This cytokine is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by Th1 CD4 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops. |
| 107 | 17981204 | The epigenetic modifications and three-dimensional structure of the Ifng locus in naive CD4 T cells, and the modifications they undergo as these cells differentiate into effector T cells, suggest a model whereby the chromatin architecture of Ifng is poised to facilitate either rapid opening or silencing during Th1 or Th2 differentiation, respectively. |
| 108 | 17981204 | This cytokine is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by Th1 CD4 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops. |
| 109 | 17981204 | The epigenetic modifications and three-dimensional structure of the Ifng locus in naive CD4 T cells, and the modifications they undergo as these cells differentiate into effector T cells, suggest a model whereby the chromatin architecture of Ifng is poised to facilitate either rapid opening or silencing during Th1 or Th2 differentiation, respectively. |
| 110 | 17989360 | We have found that, in response to interferon gamma (IFNG), mouse Sertoli cells strongly up-regulate the negative co-stimulatory ligand B7-H1 but remain devoid of positive co-stimulatory molecules. |
| 111 | 17989360 | Blockade of B7-H1 on the Sertoli cell surface resulted in enhanced proliferation of CD8(+) T cells cocultured with Sertoli cells. |
| 112 | 17989360 | Moreover, IFNG-stimulated Sertoli cells were found to express, concurrent with B7-H1, MHC class II. |
| 113 | 17989360 | Interestingly, we found that coculturing T cells with Sertoli cells can indeed induce an increase in CD4(+)CD25(+)(officially known as IL2RA)FOXP3(+) Tregs and a decrease in CD4(+)CD25(-) T cells, suggesting Sertoli cell-mediated Treg conversion; this process was found to be B7-H1-independent. |
| 114 | 17989360 | Altogether these data show that Sertoli cells are potentially capable of down-regulating the local immune response, on one hand by directly inhibiting CD8(+) T cell proliferation through B7-H1 and, on the other hand, by inducing an increase in Tregs that might suppress other bystander T cells. |
| 115 | 18406471 | Therefore, our data do not confirm a role for CD4 T-lymphocytes in protection, since there is no correlation between IFN-g secretion (supposed to be mainly derived from CD4 T-cells) and disease severity. |
| 116 | 18406471 | Additionally, we applied immunocytochemistry on affected lung tissue and detected no build up of T-lymphocytes (CD4 T-cells, CD8 T-cells) but a high presence of myeloid cells. |
| 117 | 18406471 | Therefore, our data do not confirm a role for CD4 T-lymphocytes in protection, since there is no correlation between IFN-g secretion (supposed to be mainly derived from CD4 T-cells) and disease severity. |
| 118 | 18406471 | Additionally, we applied immunocytochemistry on affected lung tissue and detected no build up of T-lymphocytes (CD4 T-cells, CD8 T-cells) but a high presence of myeloid cells. |
| 119 | 18549798 | Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation. |
| 120 | 18549798 | Differentiation of naive CD4+ T cells into T helper type 1 (Th1) effector cells requires both T cell receptor (TCR) signaling and cytokines such as interleukin-12 and interferon gamma (IFN-gamma). |
| 121 | 18549798 | Here, we report that a third cytokine signal, mediated by the Janus family tyrosine kinase 3 (Jak3) and signal transducer and activator of transcription 5 (STAT5) pathway, is also required for Th1 cell differentiation. |
| 122 | 18549798 | In the absence of Jak3-dependent signals, naive CD4+ T cells proliferate robustly but produce little IFN-gamma after Th1 cell polarization in vitro. |
| 123 | 18549798 | This defect is not due to reduced activation of STAT1 or STAT4 or to impaired upregulation of the transcription factor T-bet. |
| 124 | 18549798 | Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation. |
| 125 | 18549798 | These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation. |
| 126 | 18549798 | Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation. |
| 127 | 18549798 | Differentiation of naive CD4+ T cells into T helper type 1 (Th1) effector cells requires both T cell receptor (TCR) signaling and cytokines such as interleukin-12 and interferon gamma (IFN-gamma). |
| 128 | 18549798 | Here, we report that a third cytokine signal, mediated by the Janus family tyrosine kinase 3 (Jak3) and signal transducer and activator of transcription 5 (STAT5) pathway, is also required for Th1 cell differentiation. |
| 129 | 18549798 | In the absence of Jak3-dependent signals, naive CD4+ T cells proliferate robustly but produce little IFN-gamma after Th1 cell polarization in vitro. |
| 130 | 18549798 | This defect is not due to reduced activation of STAT1 or STAT4 or to impaired upregulation of the transcription factor T-bet. |
| 131 | 18549798 | Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation. |
| 132 | 18549798 | These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation. |
| 133 | 18684979 | Surprisingly, human naive CD4(+) T lymphocytes displayed hypermethylation at the IFNG promoter region, which is in sharp contrast to the completely demethylated status of this region in mice. |
| 134 | 18684979 | Furthermore, CD19(+) B lymphocytes displayed hypomethylation at the IFNG promoter region with a similar pattern to Th1 effector cells. |
| 135 | 18684979 | We conclude that there are obvious interspecies differences in the methylation status of the IFNG gene in naive CD4(+) T lymphocytes, where Th1 commitment in human lymphocytes involves demethylation before IFNG expression. |
| 136 | 18684979 | Surprisingly, human naive CD4(+) T lymphocytes displayed hypermethylation at the IFNG promoter region, which is in sharp contrast to the completely demethylated status of this region in mice. |
| 137 | 18684979 | Furthermore, CD19(+) B lymphocytes displayed hypomethylation at the IFNG promoter region with a similar pattern to Th1 effector cells. |
| 138 | 18684979 | We conclude that there are obvious interspecies differences in the methylation status of the IFNG gene in naive CD4(+) T lymphocytes, where Th1 commitment in human lymphocytes involves demethylation before IFNG expression. |
| 139 | 19234226 | End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. |
| 140 | 19234226 | The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. |
| 141 | 19234226 | In Tgfb1(-/-) liver, CD4(+) T cells were more numerous than CD8(+) T cells and NK cells, and produced more IFN-gamma. |
| 142 | 19234226 | Depletion of CD4(+) T cells eliminated both the elevation in plasma IFN-gamma and aspartate aminotransferase, whereas depletion of CD8(+) T cells did not. |
| 143 | 19234226 | Rag1(-/-)Tgfb1(-/-) mice exhibited neither IFN-gamma elevation nor tissue damage, indicating that NK cells are not sufficient. |
| 144 | 19234226 | IFN-gamma was required for strong overexpression of class II genes but not for CD4(+) T cell activation, oligoclonal expansion, or accumulation in the liver. |
| 145 | 19234226 | Finally, whereas Tgfb1(-/-) CD4(+) T cells overexpressed Fas ligand, hepatocellular damage was observed in Fas(lpr/lpr)Tgfb1(-/-) mice, indicating that liver pathology is Fas independent. |
| 146 | 19234226 | We conclude that liver damage in this model of fulminant autoimmune hepatitis is driven by CD4(+) T cell production of IFN-gamma, is independent of both CD8(+) T cells and the Fas ligand/Fas pathway, and is not explained by a lack of PD-L1 expression. |
| 147 | 19234226 | End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. |
| 148 | 19234226 | The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. |
| 149 | 19234226 | In Tgfb1(-/-) liver, CD4(+) T cells were more numerous than CD8(+) T cells and NK cells, and produced more IFN-gamma. |
| 150 | 19234226 | Depletion of CD4(+) T cells eliminated both the elevation in plasma IFN-gamma and aspartate aminotransferase, whereas depletion of CD8(+) T cells did not. |
| 151 | 19234226 | Rag1(-/-)Tgfb1(-/-) mice exhibited neither IFN-gamma elevation nor tissue damage, indicating that NK cells are not sufficient. |
| 152 | 19234226 | IFN-gamma was required for strong overexpression of class II genes but not for CD4(+) T cell activation, oligoclonal expansion, or accumulation in the liver. |
| 153 | 19234226 | Finally, whereas Tgfb1(-/-) CD4(+) T cells overexpressed Fas ligand, hepatocellular damage was observed in Fas(lpr/lpr)Tgfb1(-/-) mice, indicating that liver pathology is Fas independent. |
| 154 | 19234226 | We conclude that liver damage in this model of fulminant autoimmune hepatitis is driven by CD4(+) T cell production of IFN-gamma, is independent of both CD8(+) T cells and the Fas ligand/Fas pathway, and is not explained by a lack of PD-L1 expression. |
| 155 | 19234226 | End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. |
| 156 | 19234226 | The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. |
| 157 | 19234226 | In Tgfb1(-/-) liver, CD4(+) T cells were more numerous than CD8(+) T cells and NK cells, and produced more IFN-gamma. |
| 158 | 19234226 | Depletion of CD4(+) T cells eliminated both the elevation in plasma IFN-gamma and aspartate aminotransferase, whereas depletion of CD8(+) T cells did not. |
| 159 | 19234226 | Rag1(-/-)Tgfb1(-/-) mice exhibited neither IFN-gamma elevation nor tissue damage, indicating that NK cells are not sufficient. |
| 160 | 19234226 | IFN-gamma was required for strong overexpression of class II genes but not for CD4(+) T cell activation, oligoclonal expansion, or accumulation in the liver. |
| 161 | 19234226 | Finally, whereas Tgfb1(-/-) CD4(+) T cells overexpressed Fas ligand, hepatocellular damage was observed in Fas(lpr/lpr)Tgfb1(-/-) mice, indicating that liver pathology is Fas independent. |
| 162 | 19234226 | We conclude that liver damage in this model of fulminant autoimmune hepatitis is driven by CD4(+) T cell production of IFN-gamma, is independent of both CD8(+) T cells and the Fas ligand/Fas pathway, and is not explained by a lack of PD-L1 expression. |
| 163 | 19234226 | End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. |
| 164 | 19234226 | The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. |
| 165 | 19234226 | In Tgfb1(-/-) liver, CD4(+) T cells were more numerous than CD8(+) T cells and NK cells, and produced more IFN-gamma. |
| 166 | 19234226 | Depletion of CD4(+) T cells eliminated both the elevation in plasma IFN-gamma and aspartate aminotransferase, whereas depletion of CD8(+) T cells did not. |
| 167 | 19234226 | Rag1(-/-)Tgfb1(-/-) mice exhibited neither IFN-gamma elevation nor tissue damage, indicating that NK cells are not sufficient. |
| 168 | 19234226 | IFN-gamma was required for strong overexpression of class II genes but not for CD4(+) T cell activation, oligoclonal expansion, or accumulation in the liver. |
| 169 | 19234226 | Finally, whereas Tgfb1(-/-) CD4(+) T cells overexpressed Fas ligand, hepatocellular damage was observed in Fas(lpr/lpr)Tgfb1(-/-) mice, indicating that liver pathology is Fas independent. |
| 170 | 19234226 | We conclude that liver damage in this model of fulminant autoimmune hepatitis is driven by CD4(+) T cell production of IFN-gamma, is independent of both CD8(+) T cells and the Fas ligand/Fas pathway, and is not explained by a lack of PD-L1 expression. |
| 171 | 19234226 | End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. |
| 172 | 19234226 | The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. |
| 173 | 19234226 | In Tgfb1(-/-) liver, CD4(+) T cells were more numerous than CD8(+) T cells and NK cells, and produced more IFN-gamma. |
| 174 | 19234226 | Depletion of CD4(+) T cells eliminated both the elevation in plasma IFN-gamma and aspartate aminotransferase, whereas depletion of CD8(+) T cells did not. |
| 175 | 19234226 | Rag1(-/-)Tgfb1(-/-) mice exhibited neither IFN-gamma elevation nor tissue damage, indicating that NK cells are not sufficient. |
| 176 | 19234226 | IFN-gamma was required for strong overexpression of class II genes but not for CD4(+) T cell activation, oligoclonal expansion, or accumulation in the liver. |
| 177 | 19234226 | Finally, whereas Tgfb1(-/-) CD4(+) T cells overexpressed Fas ligand, hepatocellular damage was observed in Fas(lpr/lpr)Tgfb1(-/-) mice, indicating that liver pathology is Fas independent. |
| 178 | 19234226 | We conclude that liver damage in this model of fulminant autoimmune hepatitis is driven by CD4(+) T cell production of IFN-gamma, is independent of both CD8(+) T cells and the Fas ligand/Fas pathway, and is not explained by a lack of PD-L1 expression. |
| 179 | 19234226 | End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. |
| 180 | 19234226 | The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. |
| 181 | 19234226 | In Tgfb1(-/-) liver, CD4(+) T cells were more numerous than CD8(+) T cells and NK cells, and produced more IFN-gamma. |
| 182 | 19234226 | Depletion of CD4(+) T cells eliminated both the elevation in plasma IFN-gamma and aspartate aminotransferase, whereas depletion of CD8(+) T cells did not. |
| 183 | 19234226 | Rag1(-/-)Tgfb1(-/-) mice exhibited neither IFN-gamma elevation nor tissue damage, indicating that NK cells are not sufficient. |
| 184 | 19234226 | IFN-gamma was required for strong overexpression of class II genes but not for CD4(+) T cell activation, oligoclonal expansion, or accumulation in the liver. |
| 185 | 19234226 | Finally, whereas Tgfb1(-/-) CD4(+) T cells overexpressed Fas ligand, hepatocellular damage was observed in Fas(lpr/lpr)Tgfb1(-/-) mice, indicating that liver pathology is Fas independent. |
| 186 | 19234226 | We conclude that liver damage in this model of fulminant autoimmune hepatitis is driven by CD4(+) T cell production of IFN-gamma, is independent of both CD8(+) T cells and the Fas ligand/Fas pathway, and is not explained by a lack of PD-L1 expression. |
| 187 | 19234226 | End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. |
| 188 | 19234226 | The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. |
| 189 | 19234226 | In Tgfb1(-/-) liver, CD4(+) T cells were more numerous than CD8(+) T cells and NK cells, and produced more IFN-gamma. |
| 190 | 19234226 | Depletion of CD4(+) T cells eliminated both the elevation in plasma IFN-gamma and aspartate aminotransferase, whereas depletion of CD8(+) T cells did not. |
| 191 | 19234226 | Rag1(-/-)Tgfb1(-/-) mice exhibited neither IFN-gamma elevation nor tissue damage, indicating that NK cells are not sufficient. |
| 192 | 19234226 | IFN-gamma was required for strong overexpression of class II genes but not for CD4(+) T cell activation, oligoclonal expansion, or accumulation in the liver. |
| 193 | 19234226 | Finally, whereas Tgfb1(-/-) CD4(+) T cells overexpressed Fas ligand, hepatocellular damage was observed in Fas(lpr/lpr)Tgfb1(-/-) mice, indicating that liver pathology is Fas independent. |
| 194 | 19234226 | We conclude that liver damage in this model of fulminant autoimmune hepatitis is driven by CD4(+) T cell production of IFN-gamma, is independent of both CD8(+) T cells and the Fas ligand/Fas pathway, and is not explained by a lack of PD-L1 expression. |
| 195 | 19269042 | The Decoy Receptor 3 (DcR3) is known to compete with the signalling receptors of the Fas ligand (FasL), LIGHT and the TNF-like molecule 1A (TL1A). |
| 196 | 19269042 | Treatment of PLP-specific lymph node cells with DcR3.Fc protein resulted in a suppression of IFN-g and IL-17, in a reduced proportion of Th17 cells and in a decrease of encephalitogenicity. |
| 197 | 19269042 | The Th17 response promoting cytokines IL-6 and IL-23 were suppressed by DcR3.Fc as well. |
| 198 | 19269042 | DcR3.Fc-treatment of CD4+ T cells with a defective FasL did not influence the production of IL-17 indicating that DcR3 suppresses IL-17 production by disruption of Fas-FasL interactions. |
| 199 | 19384057 | Recently, we reported a novel mechanism by which the T-box transcription factor T-bet interacts with JMJD3, an H3K27-demethylase, and Set7/9, an H3K4-methyltransferase (Genes Dev. 2008. 22: 2980-2993). |
| 200 | 19384057 | Therefore, studies examining the molecular mechanisms that account for the ability of T-bet to regulate Ifng and Cxcr3, prototypic CD4+ Th1 genes, have provided novel insight into essential regulatory events that occur at diverse developmental transitions. |
| 201 | 19494038 | Here, we present a comprehensive analysis of differential DNA methylation in human conventional CD4(+) T cells (Tconv) and CD4(+)CD25(+) regulatory T cells (Treg), cell types whose differentiation and function are known to be controlled by epigenetic mechanisms. |
| 202 | 19494038 | More than 100 differentially methylated regions (DMRs) were identified that are present mainly in cell type-specific genes (e.g., FOXP3, IL2RA, CTLA4, CD40LG, and IFNG) and show differential patterns of histone H3 lysine 4 methylation. |
| 203 | 19689734 | A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells. |
| 204 | 19689734 | To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential. |
| 205 | 19689734 | We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required. |
| 206 | 19689734 | Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells. |
| 207 | 19689734 | To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER). |
| 208 | 19689734 | We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential. |
| 209 | 19689734 | On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription. |
| 210 | 19689734 | Additionally, we found that T-bet is required to maintain Ifng expression. |
| 211 | 19689734 | Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential. |
| 212 | 19689734 | A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells. |
| 213 | 19689734 | To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential. |
| 214 | 19689734 | We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required. |
| 215 | 19689734 | Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells. |
| 216 | 19689734 | To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER). |
| 217 | 19689734 | We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential. |
| 218 | 19689734 | On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription. |
| 219 | 19689734 | Additionally, we found that T-bet is required to maintain Ifng expression. |
| 220 | 19689734 | Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential. |
| 221 | 19689734 | A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells. |
| 222 | 19689734 | To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential. |
| 223 | 19689734 | We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required. |
| 224 | 19689734 | Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells. |
| 225 | 19689734 | To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER). |
| 226 | 19689734 | We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential. |
| 227 | 19689734 | On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription. |
| 228 | 19689734 | Additionally, we found that T-bet is required to maintain Ifng expression. |
| 229 | 19689734 | Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential. |
| 230 | 19747638 | Interferon gamma 13-CA-repeat homozygous genotype and a low proportion of CD4(+) lymphocytes are independent risk factors for cytomegalovirus reactivation with a high number of copies in hematopoietic stem cell transplantation recipients. |
| 231 | 19747638 | Cytomegalovirus (CMV) reactivation was analyzed in 92 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) in relation to the proportion of CD4(+) lymphocytes in blood and a microsatellite polymorphism within the first intron of the interferon-gamma (IFNG) gene. |
| 232 | 19747638 | Multivariate analysis demonstrated that the IFNG 13-CA-repeat homozygous genotype (odds ratio [OR] = 0.221; P = .044), a low proportion of CD4(+) lymphocytes (OR = 0.276; P = .050), and a lack of optimal (10/10 alleles) donor-recipient HLA match (OR = 15.19; P = .006) were independent risk factors for CMV reactivation with a high number of copies. |
| 233 | 19747638 | Interferon gamma 13-CA-repeat homozygous genotype and a low proportion of CD4(+) lymphocytes are independent risk factors for cytomegalovirus reactivation with a high number of copies in hematopoietic stem cell transplantation recipients. |
| 234 | 19747638 | Cytomegalovirus (CMV) reactivation was analyzed in 92 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) in relation to the proportion of CD4(+) lymphocytes in blood and a microsatellite polymorphism within the first intron of the interferon-gamma (IFNG) gene. |
| 235 | 19747638 | Multivariate analysis demonstrated that the IFNG 13-CA-repeat homozygous genotype (odds ratio [OR] = 0.221; P = .044), a low proportion of CD4(+) lymphocytes (OR = 0.276; P = .050), and a lack of optimal (10/10 alleles) donor-recipient HLA match (OR = 15.19; P = .006) were independent risk factors for CMV reactivation with a high number of copies. |
| 236 | 19747638 | Interferon gamma 13-CA-repeat homozygous genotype and a low proportion of CD4(+) lymphocytes are independent risk factors for cytomegalovirus reactivation with a high number of copies in hematopoietic stem cell transplantation recipients. |
| 237 | 19747638 | Cytomegalovirus (CMV) reactivation was analyzed in 92 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) in relation to the proportion of CD4(+) lymphocytes in blood and a microsatellite polymorphism within the first intron of the interferon-gamma (IFNG) gene. |
| 238 | 19747638 | Multivariate analysis demonstrated that the IFNG 13-CA-repeat homozygous genotype (odds ratio [OR] = 0.221; P = .044), a low proportion of CD4(+) lymphocytes (OR = 0.276; P = .050), and a lack of optimal (10/10 alleles) donor-recipient HLA match (OR = 15.19; P = .006) were independent risk factors for CMV reactivation with a high number of copies. |
| 239 | 19828627 | Ikaros is a regulator of Il10 expression in CD4+ T cells. |
| 240 | 19828627 | Here we show that Ikaros, a zinc finger DNA-binding protein, plays an important role in the regulation of Il10 in murine CD4(+) T cells. |
| 241 | 19828627 | Upon initial stimulation of the TCR, T cells deficient in Ikaros express significantly lower levels of IL-10 compared with wild-type T cells. |
| 242 | 19828627 | In addition, under Th2 skewing conditions, which induce IL-10 production by wild-type T cells, Ikaros null T cells are unable to properly differentiate, producing only low levels of IL-10. |
| 243 | 19828627 | Expression of a dominant-negative isoform of Ikaros in wild-type Th2 cells represses IL-10 production but does not significantly alter expression levels of the genes encoding the transcription factors GATA-3 and T-bet. |
| 244 | 19828627 | Furthermore, expression of Ikaros in Ikaros null T cells restores expression of the Th2 cytokines IL-10 and IL-4 while reducing production of the Th1 cytokine, IFN-gamma. |
| 245 | 19828627 | Coexpression of Ikaros and GATA-3 further increases IL-10 production, showing that these two factors have an additive effect on activating Il10 expression. |
| 246 | 19828627 | Finally, we show that Ikaros binds to conserved regulatory regions of the Il10 gene locus in Th2 cells, supporting a direct role for Ikaros in Il10 expression. |
| 247 | 19828627 | Thus, we provide evidence for Ikaros as a regulator of Il10 and Ifng gene expression and suggest a role for Ikaros in directing lineage-specific cytokine gene activation and repression. |
| 248 | 19828627 | Ikaros is a regulator of Il10 expression in CD4+ T cells. |
| 249 | 19828627 | Here we show that Ikaros, a zinc finger DNA-binding protein, plays an important role in the regulation of Il10 in murine CD4(+) T cells. |
| 250 | 19828627 | Upon initial stimulation of the TCR, T cells deficient in Ikaros express significantly lower levels of IL-10 compared with wild-type T cells. |
| 251 | 19828627 | In addition, under Th2 skewing conditions, which induce IL-10 production by wild-type T cells, Ikaros null T cells are unable to properly differentiate, producing only low levels of IL-10. |
| 252 | 19828627 | Expression of a dominant-negative isoform of Ikaros in wild-type Th2 cells represses IL-10 production but does not significantly alter expression levels of the genes encoding the transcription factors GATA-3 and T-bet. |
| 253 | 19828627 | Furthermore, expression of Ikaros in Ikaros null T cells restores expression of the Th2 cytokines IL-10 and IL-4 while reducing production of the Th1 cytokine, IFN-gamma. |
| 254 | 19828627 | Coexpression of Ikaros and GATA-3 further increases IL-10 production, showing that these two factors have an additive effect on activating Il10 expression. |
| 255 | 19828627 | Finally, we show that Ikaros binds to conserved regulatory regions of the Il10 gene locus in Th2 cells, supporting a direct role for Ikaros in Il10 expression. |
| 256 | 19828627 | Thus, we provide evidence for Ikaros as a regulator of Il10 and Ifng gene expression and suggest a role for Ikaros in directing lineage-specific cytokine gene activation and repression. |
| 257 | 20018909 | Blood and decidual CD4(+) T cells from 18 healthy first-trimester pregnant women were analyzed for expression of Treg-cell markers (CD25, FOXP3, CD127, CTLA4, and human leukocyte antigen-DR [HLA-DR]), chemokine receptors (CCR4, CCR6, and CXCR3), and the proliferation antigen MKI67 by six-color flow cytometry. |
| 258 | 20018909 | Using chemokine receptor expression profiles of CCR4, CCR6, and CXCR3 as markers for T(H)1, T(H)2, and T(H)17 cells, we showed that T(H)17 cells were nearly absent in decidua, whereas T(H)2-cell frequencies were similar in blood and decidua. |
| 259 | 20018909 | CCR6(+) T(H)1 cells, reported to secrete high levels of interferon gamma (IFNG), were fewer, whereas the moderately IFNG-secreting CCR6(-) T(H)1 cells were more frequent in decidua compared with blood. |
| 260 | 20304822 | Activating transcription factor 3 is a positive regulator of human IFNG gene expression. |
| 261 | 20304822 | IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-alpha in Th1 development is less understood. |
| 262 | 20304822 | In this microarray-based study, we searched for genes that are regulated by IFN-alpha, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4(+) Th cells. |
| 263 | 20304822 | Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-alpha, or the combination of IL-12 plus IL-18. |
| 264 | 20304822 | Ectopic expression of ATF3 in CD4(+) T cells enhanced the production of IFN-gamma, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-gamma production. |
| 265 | 20304822 | Furthermore, ATF3 formed an endogenous complex with JUN in CD4(+) T cells induced to Th1. |
| 266 | 20304822 | Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. |
| 267 | 20304822 | Activating transcription factor 3 is a positive regulator of human IFNG gene expression. |
| 268 | 20304822 | IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-alpha in Th1 development is less understood. |
| 269 | 20304822 | In this microarray-based study, we searched for genes that are regulated by IFN-alpha, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4(+) Th cells. |
| 270 | 20304822 | Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-alpha, or the combination of IL-12 plus IL-18. |
| 271 | 20304822 | Ectopic expression of ATF3 in CD4(+) T cells enhanced the production of IFN-gamma, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-gamma production. |
| 272 | 20304822 | Furthermore, ATF3 formed an endogenous complex with JUN in CD4(+) T cells induced to Th1. |
| 273 | 20304822 | Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. |
| 274 | 20304822 | Activating transcription factor 3 is a positive regulator of human IFNG gene expression. |
| 275 | 20304822 | IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-alpha in Th1 development is less understood. |
| 276 | 20304822 | In this microarray-based study, we searched for genes that are regulated by IFN-alpha, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4(+) Th cells. |
| 277 | 20304822 | Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-alpha, or the combination of IL-12 plus IL-18. |
| 278 | 20304822 | Ectopic expression of ATF3 in CD4(+) T cells enhanced the production of IFN-gamma, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-gamma production. |
| 279 | 20304822 | Furthermore, ATF3 formed an endogenous complex with JUN in CD4(+) T cells induced to Th1. |
| 280 | 20304822 | Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. |
| 281 | 20346061 | In kidney allografts, T cell mediated rejection (TCMR) is characterized by infiltration of the interstitium by T cells and macrophages, intense IFNG and TGFB effects, and epithelial deterioration. |
| 282 | 20346061 | This event creates the inflammatory compartment that recruits effector and effector memory CD4 and CD8 T cells, both cognate and noncognate, and macrophage precursors. |
| 283 | 20399120 | The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma. |
| 284 | 20399120 | The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells. |
| 285 | 20399120 | Here, we show that deletion of Gata3 allowed the appearance of interferon-gamma (IFN-gamma)-producing cells in the absence of interleukin-12 (IL-12) and IFN-gamma. |
| 286 | 20399120 | Such IFN-gamma production was transcription factor T-bet independent. |
| 287 | 20399120 | Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4(+) T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-gamma production. |
| 288 | 20399120 | GATA3 overexpression blocked Runx3-mediated Eomes induction and IFN-gamma production, and GATA3 protein physically interacted with Runx3 protein. |
| 289 | 20399120 | Furthermore, we found that Runx3 directly bound to multiple regulatory elements of the Ifng gene and that blocking Runx3 function in either Th1 or GATA3-deficient "Th2" cells results in diminished IFN-gamma production by these cells. |
| 290 | 20399120 | Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-gamma production in a STAT4- and T-bet-independent manner. |
| 291 | 20399120 | The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma. |
| 292 | 20399120 | The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells. |
| 293 | 20399120 | Here, we show that deletion of Gata3 allowed the appearance of interferon-gamma (IFN-gamma)-producing cells in the absence of interleukin-12 (IL-12) and IFN-gamma. |
| 294 | 20399120 | Such IFN-gamma production was transcription factor T-bet independent. |
| 295 | 20399120 | Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4(+) T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-gamma production. |
| 296 | 20399120 | GATA3 overexpression blocked Runx3-mediated Eomes induction and IFN-gamma production, and GATA3 protein physically interacted with Runx3 protein. |
| 297 | 20399120 | Furthermore, we found that Runx3 directly bound to multiple regulatory elements of the Ifng gene and that blocking Runx3 function in either Th1 or GATA3-deficient "Th2" cells results in diminished IFN-gamma production by these cells. |
| 298 | 20399120 | Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-gamma production in a STAT4- and T-bet-independent manner. |
| 299 | 20621581 | Epinephrine-primed murine bone marrow-derived dendritic cells facilitate production of IL-17A and IL-4 but not IFN-γ by CD4+ T cells. |
| 300 | 20621581 | Epinephrine pre-treatment enhanced surface expression of MHCII, CD80 and CD86. |
| 301 | 20621581 | Epinephrine pre-treatment also induced a significant decrease of IL-12p70 and a significant increase of IL-23 and IL-10 cytokine production. |
| 302 | 20621581 | Importantly, these changes corresponded with increased IL-4 and IL-17A, but not IFN-g cytokine production by CD4(+) T cells in a b2-adrenergic receptor-dependent manner. |
| 303 | 20621581 | Epinephrine-primed murine bone marrow-derived dendritic cells facilitate production of IL-17A and IL-4 but not IFN-γ by CD4+ T cells. |
| 304 | 20621581 | Epinephrine pre-treatment enhanced surface expression of MHCII, CD80 and CD86. |
| 305 | 20621581 | Epinephrine pre-treatment also induced a significant decrease of IL-12p70 and a significant increase of IL-23 and IL-10 cytokine production. |
| 306 | 20621581 | Importantly, these changes corresponded with increased IL-4 and IL-17A, but not IFN-g cytokine production by CD4(+) T cells in a b2-adrenergic receptor-dependent manner. |
| 307 | 20709293 | Fidelity of pathogen-specific CD4+ T cells to the Th1 lineage is controlled by exogenous cytokines, interferon-gamma expression, and pathogen lifestyle. |
| 308 | 20963786 | Changes in histone acetylation and methylation that are important for persistent but not transient expression of CCR4 in human CD4+ T cells. |
| 309 | 20963786 | Although regulation of CXCR3 and CCR4 is related to Th1 and Th2 differentiation, respectively, many CXCR3(+) and CCR4(+) cells do not express IFN-γ and/or IL-4, suggesting that the chemokine receptor genes might be inducible by mechanisms that are lineage-independent. |
| 310 | 20963786 | We investigated the regulation of CXCR3 versus IFNG, and CCR4 versus IL4 in human CD4(+) T cells by analyzing modifications of histone H3. |
| 311 | 20963786 | In naïve cord-blood cells, under nonpolarizing conditions not inducing IL4, CCR4 was induced to high levels without many of the activation-associated changes in promoter histone H3 found for both IL4 and CCR4 in Th2 cells. |
| 312 | 20963786 | Patterns of histone H3 modifications in CXCR3(+) CCR4(-) and CXCR3(-) CCR4(+) CD4(+) T-cell subsets from adult blood matched those in cells cultured under polarizing conditions in vitro. |
| 313 | 20963786 | Changes in histone acetylation and methylation that are important for persistent but not transient expression of CCR4 in human CD4+ T cells. |
| 314 | 20963786 | Although regulation of CXCR3 and CCR4 is related to Th1 and Th2 differentiation, respectively, many CXCR3(+) and CCR4(+) cells do not express IFN-γ and/or IL-4, suggesting that the chemokine receptor genes might be inducible by mechanisms that are lineage-independent. |
| 315 | 20963786 | We investigated the regulation of CXCR3 versus IFNG, and CCR4 versus IL4 in human CD4(+) T cells by analyzing modifications of histone H3. |
| 316 | 20963786 | In naïve cord-blood cells, under nonpolarizing conditions not inducing IL4, CCR4 was induced to high levels without many of the activation-associated changes in promoter histone H3 found for both IL4 and CCR4 in Th2 cells. |
| 317 | 20963786 | Patterns of histone H3 modifications in CXCR3(+) CCR4(-) and CXCR3(-) CCR4(+) CD4(+) T-cell subsets from adult blood matched those in cells cultured under polarizing conditions in vitro. |
| 318 | 20963786 | Changes in histone acetylation and methylation that are important for persistent but not transient expression of CCR4 in human CD4+ T cells. |
| 319 | 20963786 | Although regulation of CXCR3 and CCR4 is related to Th1 and Th2 differentiation, respectively, many CXCR3(+) and CCR4(+) cells do not express IFN-γ and/or IL-4, suggesting that the chemokine receptor genes might be inducible by mechanisms that are lineage-independent. |
| 320 | 20963786 | We investigated the regulation of CXCR3 versus IFNG, and CCR4 versus IL4 in human CD4(+) T cells by analyzing modifications of histone H3. |
| 321 | 20963786 | In naïve cord-blood cells, under nonpolarizing conditions not inducing IL4, CCR4 was induced to high levels without many of the activation-associated changes in promoter histone H3 found for both IL4 and CCR4 in Th2 cells. |
| 322 | 20963786 | Patterns of histone H3 modifications in CXCR3(+) CCR4(-) and CXCR3(-) CCR4(+) CD4(+) T-cell subsets from adult blood matched those in cells cultured under polarizing conditions in vitro. |
| 323 | 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. |
| 324 | 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. |
| 325 | 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. |
| 326 | 21518797 | The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns. |
| 327 | 21518797 | The T-box transcription factor T-bet is important for the differentiation of naive CD4(+) T helper cells (Th cells) into the Th1 phenotype. |
| 328 | 21518797 | In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet. |
| 329 | 21518797 | Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells. |
| 330 | 21518797 | Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity. |
| 331 | 21573182 | There were no differences in early IFN-g and IL-10 expression between WT and IL-13-/- mice and depletion of CD4+ T cells did not affect infection in IL-13-/- mice. |
| 332 | 21573182 | Collectively, these data demonstrate a lack of CD4+ T cell involvement and a novel role for IL-13 in innate responses to infection. |
| 333 | 21573182 | There were no differences in early IFN-g and IL-10 expression between WT and IL-13-/- mice and depletion of CD4+ T cells did not affect infection in IL-13-/- mice. |
| 334 | 21573182 | Collectively, these data demonstrate a lack of CD4+ T cell involvement and a novel role for IL-13 in innate responses to infection. |
| 335 | 21706005 | One of the signature microRNAs of naive CD4+ T cells, miR-125b, regulated the expression of genes encoding molecules involved in T cell differentiation, including IFNG, IL2RB, IL10RA and PRDM1. |
| 336 | 21783593 | Mice were treated with DNCB and TDI showed a preferential increase in the percentage of CD4+IL-2+ cells compared with vehicle and irritant-treated mice. |
| 337 | 21783593 | There was an increase in CD4+IFN-g+ cells of mice treated with DNCB and TDI, but no significant increases were observed in mice treated with SLS. |
| 338 | 21783593 | Mice were treated with DNCB and TDI showed an increase in the percentage of CD4+IL-4+ cells compared with vehicle and irritant-treated mice. |
| 339 | 21783593 | These results suggest that the population of interferon-gamma (IFN-g+) and IL-4+ cells on CD4+ cells and the mRNA expression for IL-4 in lymphocytes could be selectively modulated in allergen-treated mice. |
| 340 | 21783593 | Mice were treated with DNCB and TDI showed a preferential increase in the percentage of CD4+IL-2+ cells compared with vehicle and irritant-treated mice. |
| 341 | 21783593 | There was an increase in CD4+IFN-g+ cells of mice treated with DNCB and TDI, but no significant increases were observed in mice treated with SLS. |
| 342 | 21783593 | Mice were treated with DNCB and TDI showed an increase in the percentage of CD4+IL-4+ cells compared with vehicle and irritant-treated mice. |
| 343 | 21783593 | These results suggest that the population of interferon-gamma (IFN-g+) and IL-4+ cells on CD4+ cells and the mRNA expression for IL-4 in lymphocytes could be selectively modulated in allergen-treated mice. |
| 344 | 21783593 | Mice were treated with DNCB and TDI showed a preferential increase in the percentage of CD4+IL-2+ cells compared with vehicle and irritant-treated mice. |
| 345 | 21783593 | There was an increase in CD4+IFN-g+ cells of mice treated with DNCB and TDI, but no significant increases were observed in mice treated with SLS. |
| 346 | 21783593 | Mice were treated with DNCB and TDI showed an increase in the percentage of CD4+IL-4+ cells compared with vehicle and irritant-treated mice. |
| 347 | 21783593 | These results suggest that the population of interferon-gamma (IFN-g+) and IL-4+ cells on CD4+ cells and the mRNA expression for IL-4 in lymphocytes could be selectively modulated in allergen-treated mice. |
| 348 | 21783593 | Mice were treated with DNCB and TDI showed a preferential increase in the percentage of CD4+IL-2+ cells compared with vehicle and irritant-treated mice. |
| 349 | 21783593 | There was an increase in CD4+IFN-g+ cells of mice treated with DNCB and TDI, but no significant increases were observed in mice treated with SLS. |
| 350 | 21783593 | Mice were treated with DNCB and TDI showed an increase in the percentage of CD4+IL-4+ cells compared with vehicle and irritant-treated mice. |
| 351 | 21783593 | These results suggest that the population of interferon-gamma (IFN-g+) and IL-4+ cells on CD4+ cells and the mRNA expression for IL-4 in lymphocytes could be selectively modulated in allergen-treated mice. |
| 352 | 21983879 | T-bet orchestrates the differentiation of mature peripheral T-cells into interferon-γ (IFN-γ) and tumor necrosis factor-α producing CD4+ T-helper type I (Th1) and CD8+ T cytotoxic cells that are necessary for antiviral responses. |
| 353 | 21983879 | When IL-12 is produced by antigen-presenting cells, T-bet expression is induced, causing direct stimulation of ifng gene transcription while simultaneously acting as a transcriptional repressor of the IL4 gene, which then leads to Th1 dominance and T-helper type 2 differentiation blockade. |
| 354 | 21983879 | We found that treatment with a farnesyltransferase inhibitor tipifarnib reduced Th1 cytokines in LGL leukemia patient T-cells and blocked T-bet protein expression and IL-12 responsiveness in T-cells from healthy donors. |
| 355 | 22407948 | Previous studies have shown that short-term (4 weeks) or chronic (32 weeks) exposure to trichloroethylene (TCE) in drinking water of female MRL+/+ mice generated CD4(+) T cells that secreted increased levels of interferon (IFN)-γ and expressed an activated (CD44(hi)CD62L(lo)) phenotype. |
| 356 | 22407948 | Also observed was an increase in the expression of Dnmt1 (DNA methyltransferase-1) and decreased expression of several genes known to be downregulated by DNA methylation, namely Ifng, Il2, and Cdkn1a. |
| 357 | 22407948 | CD4(+) T cells from a second study in which MRL+/+ mice were treated for 17 weeks with TCE showed a similar increase in Iap and decrease in Cdkn1a. |
| 358 | 22407948 | Previous studies have shown that short-term (4 weeks) or chronic (32 weeks) exposure to trichloroethylene (TCE) in drinking water of female MRL+/+ mice generated CD4(+) T cells that secreted increased levels of interferon (IFN)-γ and expressed an activated (CD44(hi)CD62L(lo)) phenotype. |
| 359 | 22407948 | Also observed was an increase in the expression of Dnmt1 (DNA methyltransferase-1) and decreased expression of several genes known to be downregulated by DNA methylation, namely Ifng, Il2, and Cdkn1a. |
| 360 | 22407948 | CD4(+) T cells from a second study in which MRL+/+ mice were treated for 17 weeks with TCE showed a similar increase in Iap and decrease in Cdkn1a. |
| 361 | 22578563 | To test this hypothesis, mice deficient in genes regulating IFN-γ expression (Casp1, Nlrp3, Il12a, Il12b, Stat4) or function (Ifngr1, Irf1) were examined for mHgIA susceptibility. |
| 362 | 22578563 | Absence of either Ifngr1 or Irf1 resulted in a striking reduction of disease, while deficiency of genes promoting IFN-γ expression had modest to no effect. |
| 363 | 22578563 | Furthermore, both Irf1- and Ifng-deficiency only modestly reduced the expansion of CD44(hi) and CD44(hi)CD55(lo) CD4(+) T cells, indicating that they are not absolutely required for T cell activation. |
| 364 | 22649557 | Interestingly, the latter delay or protection from T1D is associated with the enhanced secretion of IL-10 rather than IFN-g by C24:0-treated CD4(+) T cells and the deviation of the islet-reactive diabetogenic T cell response. |
| 365 | 22837486 | CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection. |
| 366 | 22837486 | Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-γ. |
| 367 | 22837486 | We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo, and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-γ in the lungs. |
| 368 | 22837486 | In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-γ in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-γ production by CD8+ effector cells. |
| 369 | 22837486 | Accordingly, when infected mice were treated i.v. with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. |
| 370 | 22837486 | Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells but independent of IFN-g responsiveness of the CD8+ cells. |
| 371 | 22837486 | These data provide evidence that CD4+ cell deficiency impairs IFN-γ production by CD8+ effector cells and that ongoing cross-talk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. |
| 372 | 22837486 | CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection. |
| 373 | 22837486 | Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-γ. |
| 374 | 22837486 | We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo, and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-γ in the lungs. |
| 375 | 22837486 | In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-γ in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-γ production by CD8+ effector cells. |
| 376 | 22837486 | Accordingly, when infected mice were treated i.v. with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. |
| 377 | 22837486 | Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells but independent of IFN-g responsiveness of the CD8+ cells. |
| 378 | 22837486 | These data provide evidence that CD4+ cell deficiency impairs IFN-γ production by CD8+ effector cells and that ongoing cross-talk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. |
| 379 | 22837486 | CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection. |
| 380 | 22837486 | Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-γ. |
| 381 | 22837486 | We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo, and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-γ in the lungs. |
| 382 | 22837486 | In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-γ in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-γ production by CD8+ effector cells. |
| 383 | 22837486 | Accordingly, when infected mice were treated i.v. with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. |
| 384 | 22837486 | Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells but independent of IFN-g responsiveness of the CD8+ cells. |
| 385 | 22837486 | These data provide evidence that CD4+ cell deficiency impairs IFN-γ production by CD8+ effector cells and that ongoing cross-talk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. |
| 386 | 22837486 | CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection. |
| 387 | 22837486 | Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-γ. |
| 388 | 22837486 | We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo, and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-γ in the lungs. |
| 389 | 22837486 | In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-γ in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-γ production by CD8+ effector cells. |
| 390 | 22837486 | Accordingly, when infected mice were treated i.v. with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. |
| 391 | 22837486 | Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells but independent of IFN-g responsiveness of the CD8+ cells. |
| 392 | 22837486 | These data provide evidence that CD4+ cell deficiency impairs IFN-γ production by CD8+ effector cells and that ongoing cross-talk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. |
| 393 | 22837486 | CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection. |
| 394 | 22837486 | Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-γ. |
| 395 | 22837486 | We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo, and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-γ in the lungs. |
| 396 | 22837486 | In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-γ in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-γ production by CD8+ effector cells. |
| 397 | 22837486 | Accordingly, when infected mice were treated i.v. with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. |
| 398 | 22837486 | Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells but independent of IFN-g responsiveness of the CD8+ cells. |
| 399 | 22837486 | These data provide evidence that CD4+ cell deficiency impairs IFN-γ production by CD8+ effector cells and that ongoing cross-talk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. |
| 400 | 22837486 | CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection. |
| 401 | 22837486 | Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-γ. |
| 402 | 22837486 | We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo, and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-γ in the lungs. |
| 403 | 22837486 | In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-γ in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-γ production by CD8+ effector cells. |
| 404 | 22837486 | Accordingly, when infected mice were treated i.v. with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. |
| 405 | 22837486 | Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells but independent of IFN-g responsiveness of the CD8+ cells. |
| 406 | 22837486 | These data provide evidence that CD4+ cell deficiency impairs IFN-γ production by CD8+ effector cells and that ongoing cross-talk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. |
| 407 | 22837486 | CD4+ T cell-dependent IFN-γ production by CD8+ effector T cells in Mycobacterium tuberculosis infection. |
| 408 | 22837486 | Both CD4+ and CD8+ T cells contribute to immunity to tuberculosis, and both can produce the essential effector cytokine IFN-γ. |
| 409 | 22837486 | We found that CD4+ and CD8+ cells were predominantly responsible for production of this cytokine in vivo, and we observed a remarkable linear correlation between the fraction of CD4+ cells and the fraction of CD8+ cells producing IFN-γ in the lungs. |
| 410 | 22837486 | In the absence of CD4+ cells, a reduced fraction of CD8+ cells was actively producing IFN-γ in vivo, suggesting that CD4+ effector cells are continually required for optimal IFN-γ production by CD8+ effector cells. |
| 411 | 22837486 | Accordingly, when infected mice were treated i.v. with an MHC-II-restricted M. tuberculosis epitope peptide to stimulate CD4+ cells in vivo, we observed rapid activation of both CD4+ and CD8+ cells in the lungs. |
| 412 | 22837486 | Indirect activation of CD8+ cells was dependent on the presence of CD4+ cells but independent of IFN-g responsiveness of the CD8+ cells. |
| 413 | 22837486 | These data provide evidence that CD4+ cell deficiency impairs IFN-γ production by CD8+ effector cells and that ongoing cross-talk between distinct effector T cell types in the lungs may contribute to a protective immune response against M. tuberculosis. |
| 414 | 22842304 | Schistosoma mansoni schistosomula tegument (Smteg) immunization in absence of adjuvant induce IL-10 production by CD4+ cells and failed to protect mice against challenge infection. |
| 415 | 22842304 | Smteg mice immunization resulted in significant antibody production, increased percentage of CD4+IFN-g+ and CD4+IL-10+ cells in spleen and increased production of IFN-g and IL-10 by spleen cells, but failed to reduce parasite burden, female fecundity and morbidity. |
| 416 | 22842304 | Schistosoma mansoni schistosomula tegument (Smteg) immunization in absence of adjuvant induce IL-10 production by CD4+ cells and failed to protect mice against challenge infection. |
| 417 | 22842304 | Smteg mice immunization resulted in significant antibody production, increased percentage of CD4+IFN-g+ and CD4+IL-10+ cells in spleen and increased production of IFN-g and IL-10 by spleen cells, but failed to reduce parasite burden, female fecundity and morbidity. |
| 418 | 23063468 | Therefore, the DNA methylation status of the Ifng promoter in CD4(+) cells from neonatal foal was determined using a methylation-specific PCR (MSP), and its relevance to IFN-γ mRNA expression was estimated. |
| 419 | 23144609 | Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions. |
| 420 | 23144609 | T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. |
| 421 | 23144609 | Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells, which preferentially displayed polarized effector memory phenotypes. |
| 422 | 23144609 | Consistent with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more apparently limited intracellular Mtb replication in macrophages. |
| 423 | 23144609 | The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. |
| 424 | 23144609 | Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. |
| 425 | 23144609 | Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions. |
| 426 | 23144609 | T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. |
| 427 | 23144609 | Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells, which preferentially displayed polarized effector memory phenotypes. |
| 428 | 23144609 | Consistent with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more apparently limited intracellular Mtb replication in macrophages. |
| 429 | 23144609 | The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. |
| 430 | 23144609 | Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. |
| 431 | 23144609 | Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions. |
| 432 | 23144609 | T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. |
| 433 | 23144609 | Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells, which preferentially displayed polarized effector memory phenotypes. |
| 434 | 23144609 | Consistent with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more apparently limited intracellular Mtb replication in macrophages. |
| 435 | 23144609 | The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. |
| 436 | 23144609 | Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. |
| 437 | 23144609 | Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions. |
| 438 | 23144609 | T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. |
| 439 | 23144609 | Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells, which preferentially displayed polarized effector memory phenotypes. |
| 440 | 23144609 | Consistent with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more apparently limited intracellular Mtb replication in macrophages. |
| 441 | 23144609 | The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. |
| 442 | 23144609 | Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. |
| 443 | 23144609 | Tim-3-expressing CD4+ and CD8+ T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions. |
| 444 | 23144609 | T-cell immune responses modulated by T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. |
| 445 | 23144609 | Here, we found that active TB patients exhibited increases in numbers of Tim-3-expressing CD4(+) and CD8(+) T cells, which preferentially displayed polarized effector memory phenotypes. |
| 446 | 23144609 | Consistent with effector phenotypes, Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets showed greater effector functions for producing Th1/Th22 cytokines and CTL effector molecules than Tim-3(-) counterparts, and Tim-3-expressing T cells more apparently limited intracellular Mtb replication in macrophages. |
| 447 | 23144609 | The increased effector functions for Tim-3-expressing T cells consisted with cellular activation signaling as Tim-3(+)CD4(+) and Tim-3(+)CD8(+) T-cell subsets expressed much higher levels of phosphorylated signaling molecules p38, stat3, stat5, and Erk1/2 than Tim-3- controls. |
| 448 | 23144609 | Furthermore, stimulation of Tim-3 signaling pathways by antibody cross-linking of membrane Tim-3 augmented effector function of IFN-γ production by CD4(+) and CD8(+) T cells, suggesting that Tim-3 signaling helped to drive stronger effector functions in active TB patients. |
| 449 | 23255246 | Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-γ memory in human CD4(+) T lymphocytes. |
| 450 | 23459632 | The number of bone marrow MSCs inversely correlated with the number of both CD4 and CD8 T cells present in the bone marrow indicating a link between activated T cells and MSC mobilization. |
| 451 | 23464355 | Interleukin-27 (IL-27) is a heterodimeric cytokine of the IL-12 family that is produced primarily by antigen-presenting cells and is immunosuppressive toward a variety of immune cell types. |
| 452 | 23464355 | We show that IL-27 gene expression is elevated in cord blood-derived macrophages relative to macrophages originating from healthy adults. |
| 453 | 23464355 | We also evaluated the duration over which elevated IL-27 gene expression may impact immune responses in mice. |
| 454 | 23464355 | Age-dependent analysis of IL-27 gene expression indicated that levels of IL-27 remained significantly elevated throughout infancy and then declined in adult mice. |
| 455 | 23464355 | Neutralization of IL-27 in neonatal macrophages improved the ability of these cells to limit bacterial replication. |
| 456 | 23464355 | Moreover, neutralization of IL-27 during incubation with the Mycobacterium bovis bacillus Calmette-Guérin vaccine augmented the level of interferon-γ elicited from allogeneic CD4+ T lymphocytes. |
| 457 | 23464355 | This suggests that blocking IL-27 during vaccination and infection may improve immune responses in newborn and infant populations. |
| 458 | 23609452 | 60-kDa Tat-interactive protein (TIP60) positively regulates Th-inducing POK (ThPOK)-mediated repression of eomesodermin in human CD4+ T cells. |
| 459 | 23609452 | The abundant expression of IFNγ in Th-inducing POK (ThPOK)-deficient CD4(+) T cells requires the activation of Eomesodermin (Eomes); however, the underlying mechanism of this phenomenon remains unclear. |
| 460 | 23609452 | Here we report that ThPOK binds directly to the promoter region of the Eomes gene to repress its expression in CD4(+) T cells. |
| 461 | 23609452 | We identified the histone acetyltransferase TIP60 as a co-repressor of ThPOK-target genes, where ectopically expressed TIP60 increased ThPOK protein stability by promoting its acetylation at its Lys(360) residue to then augment the transcriptional repression of Eomes. |
| 462 | 23609452 | Moreover, knockdown of endogenous TIP60 abolished the stabilization of ThPOK in CD4(+) T cells, which led to the transcriptional activation of Eomes and increased production of IFNγ. |
| 463 | 23609452 | Our results reveal a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNγ production, which could contribute to the regulation of inflammation. |
| 464 | 23609452 | 60-kDa Tat-interactive protein (TIP60) positively regulates Th-inducing POK (ThPOK)-mediated repression of eomesodermin in human CD4+ T cells. |
| 465 | 23609452 | The abundant expression of IFNγ in Th-inducing POK (ThPOK)-deficient CD4(+) T cells requires the activation of Eomesodermin (Eomes); however, the underlying mechanism of this phenomenon remains unclear. |
| 466 | 23609452 | Here we report that ThPOK binds directly to the promoter region of the Eomes gene to repress its expression in CD4(+) T cells. |
| 467 | 23609452 | We identified the histone acetyltransferase TIP60 as a co-repressor of ThPOK-target genes, where ectopically expressed TIP60 increased ThPOK protein stability by promoting its acetylation at its Lys(360) residue to then augment the transcriptional repression of Eomes. |
| 468 | 23609452 | Moreover, knockdown of endogenous TIP60 abolished the stabilization of ThPOK in CD4(+) T cells, which led to the transcriptional activation of Eomes and increased production of IFNγ. |
| 469 | 23609452 | Our results reveal a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNγ production, which could contribute to the regulation of inflammation. |
| 470 | 23609452 | 60-kDa Tat-interactive protein (TIP60) positively regulates Th-inducing POK (ThPOK)-mediated repression of eomesodermin in human CD4+ T cells. |
| 471 | 23609452 | The abundant expression of IFNγ in Th-inducing POK (ThPOK)-deficient CD4(+) T cells requires the activation of Eomesodermin (Eomes); however, the underlying mechanism of this phenomenon remains unclear. |
| 472 | 23609452 | Here we report that ThPOK binds directly to the promoter region of the Eomes gene to repress its expression in CD4(+) T cells. |
| 473 | 23609452 | We identified the histone acetyltransferase TIP60 as a co-repressor of ThPOK-target genes, where ectopically expressed TIP60 increased ThPOK protein stability by promoting its acetylation at its Lys(360) residue to then augment the transcriptional repression of Eomes. |
| 474 | 23609452 | Moreover, knockdown of endogenous TIP60 abolished the stabilization of ThPOK in CD4(+) T cells, which led to the transcriptional activation of Eomes and increased production of IFNγ. |
| 475 | 23609452 | Our results reveal a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNγ production, which could contribute to the regulation of inflammation. |
| 476 | 23609452 | 60-kDa Tat-interactive protein (TIP60) positively regulates Th-inducing POK (ThPOK)-mediated repression of eomesodermin in human CD4+ T cells. |
| 477 | 23609452 | The abundant expression of IFNγ in Th-inducing POK (ThPOK)-deficient CD4(+) T cells requires the activation of Eomesodermin (Eomes); however, the underlying mechanism of this phenomenon remains unclear. |
| 478 | 23609452 | Here we report that ThPOK binds directly to the promoter region of the Eomes gene to repress its expression in CD4(+) T cells. |
| 479 | 23609452 | We identified the histone acetyltransferase TIP60 as a co-repressor of ThPOK-target genes, where ectopically expressed TIP60 increased ThPOK protein stability by promoting its acetylation at its Lys(360) residue to then augment the transcriptional repression of Eomes. |
| 480 | 23609452 | Moreover, knockdown of endogenous TIP60 abolished the stabilization of ThPOK in CD4(+) T cells, which led to the transcriptional activation of Eomes and increased production of IFNγ. |
| 481 | 23609452 | Our results reveal a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNγ production, which could contribute to the regulation of inflammation. |
| 482 | 23613752 | Interferon gamma suppresses collagen-induced arthritis by regulation of Th17 through the induction of indoleamine-2,3-deoxygenase. |
| 483 | 23613752 | C57BL/6 mice are known to be resistant to the development of collagen-induced arthritis (CIA). |
| 484 | 23613752 | Also, production of IL-17 by the splenocytes of the IFN-γ KO mice was increased when cultured with type II collagen. |
| 485 | 23613752 | The proportion of CD44(high)CD62L(low) memory-like T cells were elevated in the spleen, draining lymph node and mesenteric lymph node of IFN-γ KO CIA mice. |
| 486 | 23613752 | Meanwhile, CD44(low)CD62L(high) naïve T cells were increased in IFN-γ and IL-17 double KO CIA mice. |
| 487 | 23613752 | When Th17 polarized CD4+ T cells of IFN-γ KO mice were co-cultured with their own antigen presenting cells (APCs), a greater increase in IL-17 production was observed than in co-culture of the cells from wild type mice. |
| 488 | 23663684 | Upon dendritic cell activation in the adventitia, CD4 T cells co-expressing CD161 are recruited in the arterial wall and polarised into Th1 and Th17 cells that produce IFN-γ and IL-17, respectively. |
| 489 | 23663684 | Macrophages infiltrating the adventitia produce IL-1β and IL-6, which are responsible for the general symptoms encountered in GCA. |
| 490 | 23668260 | The infected mice displayed a significant up-regulation in the expression of chemokines (Cxcl1, Cxcl2 and Ccl2), numerous pro-inflammatory cytokines (Ifng, Il1b, Il6, and Il17f), as well as Il22 and a number of anti-microbial peptides (Defa1, Defa28, Defb1, Slpi and Reg3g) at the site(s) of infection. |
| 491 | 23668260 | However, CD4 T cells of the untreated and C. difficile-infected mice expressed similar levels of CD69 and CD25. |
| 492 | 23668260 | Neither tissue had up-regulated levels of Tbx21, Gata3 or Rorc. |
| 493 | 23668260 | They also displayed significantly higher phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), an indication of pro-survival signalling. |
| 494 | 23668260 | These data underscore the local, innate, pro-inflammatory nature of the response to C. difficile and highlight eIF2α phosphorylation and the interleukin-22-pSTAT3-RegIIIγ axis as two of the pathways that could be used to contain and counteract the damage inflicted on the intestinal epithelium. |
| 495 | 23755752 | Histone modifications of Notch1 promoter affect lung CD4+ T cell differentiation in asthmatic rats. |
| 496 | 23755752 | The present study aimed to explore the histone modifications of Notch1 promoter in normal and asthmatic lung CD4+ T cells. |
| 497 | 23755752 | Chromatin immunoprecipitation analysis showed that the acetylation levels of total H3, H4, site-specific H3K9, H3K14, H3K27, H3K18, H4K16, and the trimethylation levels of H3K4, H3K79 of Notch1 gene promoter were increased significantly in asthmatic lung CD4+ T cells compared to the control group, which correlated with increased P300, PCAF activity and decreased HDAC1, HDAC2 activity. |
| 498 | 23755752 | After intervention of garcinol, a potent inhibitor of histone acetyltransferases, in asthmatic lung CD4+ T cells, HAT activity decreased significantly and the increased Notch1 and hes-1 expression was reversed. |
| 499 | 23755752 | Results showed that the levels of IL-4, IL-5 and IL-13 were significantly reduced and a small reverse trend was found in the level of IFN-g after GAR treatment. |
| 500 | 23755752 | Histone modifications of Notch1 promoter affect lung CD4+ T cell differentiation in asthmatic rats. |
| 501 | 23755752 | The present study aimed to explore the histone modifications of Notch1 promoter in normal and asthmatic lung CD4+ T cells. |
| 502 | 23755752 | Chromatin immunoprecipitation analysis showed that the acetylation levels of total H3, H4, site-specific H3K9, H3K14, H3K27, H3K18, H4K16, and the trimethylation levels of H3K4, H3K79 of Notch1 gene promoter were increased significantly in asthmatic lung CD4+ T cells compared to the control group, which correlated with increased P300, PCAF activity and decreased HDAC1, HDAC2 activity. |
| 503 | 23755752 | After intervention of garcinol, a potent inhibitor of histone acetyltransferases, in asthmatic lung CD4+ T cells, HAT activity decreased significantly and the increased Notch1 and hes-1 expression was reversed. |
| 504 | 23755752 | Results showed that the levels of IL-4, IL-5 and IL-13 were significantly reduced and a small reverse trend was found in the level of IFN-g after GAR treatment. |
| 505 | 23755752 | Histone modifications of Notch1 promoter affect lung CD4+ T cell differentiation in asthmatic rats. |
| 506 | 23755752 | The present study aimed to explore the histone modifications of Notch1 promoter in normal and asthmatic lung CD4+ T cells. |
| 507 | 23755752 | Chromatin immunoprecipitation analysis showed that the acetylation levels of total H3, H4, site-specific H3K9, H3K14, H3K27, H3K18, H4K16, and the trimethylation levels of H3K4, H3K79 of Notch1 gene promoter were increased significantly in asthmatic lung CD4+ T cells compared to the control group, which correlated with increased P300, PCAF activity and decreased HDAC1, HDAC2 activity. |
| 508 | 23755752 | After intervention of garcinol, a potent inhibitor of histone acetyltransferases, in asthmatic lung CD4+ T cells, HAT activity decreased significantly and the increased Notch1 and hes-1 expression was reversed. |
| 509 | 23755752 | Results showed that the levels of IL-4, IL-5 and IL-13 were significantly reduced and a small reverse trend was found in the level of IFN-g after GAR treatment. |
| 510 | 23755752 | Histone modifications of Notch1 promoter affect lung CD4+ T cell differentiation in asthmatic rats. |
| 511 | 23755752 | The present study aimed to explore the histone modifications of Notch1 promoter in normal and asthmatic lung CD4+ T cells. |
| 512 | 23755752 | Chromatin immunoprecipitation analysis showed that the acetylation levels of total H3, H4, site-specific H3K9, H3K14, H3K27, H3K18, H4K16, and the trimethylation levels of H3K4, H3K79 of Notch1 gene promoter were increased significantly in asthmatic lung CD4+ T cells compared to the control group, which correlated with increased P300, PCAF activity and decreased HDAC1, HDAC2 activity. |
| 513 | 23755752 | After intervention of garcinol, a potent inhibitor of histone acetyltransferases, in asthmatic lung CD4+ T cells, HAT activity decreased significantly and the increased Notch1 and hes-1 expression was reversed. |
| 514 | 23755752 | Results showed that the levels of IL-4, IL-5 and IL-13 were significantly reduced and a small reverse trend was found in the level of IFN-g after GAR treatment. |
| 515 | 23761633 | STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation. |
| 516 | 23761633 | CD4(+) T cells developing toward a Th2 fate express IL-4, IL-5, and IL-13 while inhibiting production of cytokines associated with other Th types, such as the Th1 cytokine IFN- γ. |
| 517 | 23761633 | We now show that this flexibility ("plasticity") of cytokine expression is preceded by a loss of the repressive DNA methylation of the Ifng promoter acquired during Th2 polarization yet requires STAT4 along with T-box expressed in T cells. |
| 518 | 23761633 | Surprisingly, loss of either STAT4 or T-box expressed in T cells increased Ifng promoter CpG methylation in both effector and memory Th2 cells. |
| 519 | 23798565 | Suppression is associated with development of a regulatory population of donor CD4(+) CD25(+)T-cells that express high levels of cytotoxic T-lymphocyte antigen 4 (CTLA-4). |
| 520 | 23798565 | CTLA-4 is a negative regulator of T-cell responses and is associated with the induction of tolerogenic dendritic cells (DCs) that produce indoleamine 2,3-dioxygenase (IDO). |
| 521 | 23798565 | Here, we show that despite increased expression of Ifng, Irf3, Irf7, Ido1, and Ido2 in the lymph nodes of TCDD-treated host mice, inhibition of IDO enzyme activity by 1-methyl-tryptophan was unable to relieve TCDD-mediated suppression of the GVH response. |
| 522 | 23800749 | Furthermore, autophagy-attenuation in Hyp-PDT-treated cancer cells increased their ability to induce DC maturation, IL6 production and proliferation of CD4(+) or CD8(+) T cells, which was accompanied by IFNG production. |
| 523 | 23939944 | Here we show that human umbilical cord blood (UCB)-derived CD34+CD38-/low hematopoietic stem cells can be successfully differentiated into functional, antigen-specific cytotoxic CD8+ T cells without direct stromal coculture or retroviral TCR transfection. |
| 524 | 23939944 | Surface-immobilized Notch ligands (DLL1) and stromal cell conditioned medium successfully induced the development of CD1a+CD7+ and CD4+CD8+ early T cells. |
| 525 | 23939944 | These cells, upon continued culture with cytomegalovirus (CMV) or influenza-A virus M1 (GIL) epitope-loaded human leukocyte antigen (HLA)-A*0201 tetramers, resulted in the generation of a polyclonal population of CMV-specific or GIL-specific CD8+ T cells, respectively. |
| 526 | 23939944 | Upon further activation with antigen-loaded target cells, these antigen-specific, stem cell-derived T cells exhibited cytolytic functionality, specifically CD107a surface mobilization, interferon gamma (IFNg) production, and Granzyme B secretion. |
| 527 | 24163409 | Aggregates of activated IFN-γ- and IL-17A-secreting CD4(+) T cells as well as B cells surrounded the airways. |
| 528 | 24163409 | Lung pathology was similar in Ifng(-/-) and Il17a(-/-) mice, indicating that either cytokine is sufficient to establish chronic disease. |
| 529 | 24164838 | IL-22+ CD4+ T cells in patients with rheumatoid arthritis. |
| 530 | 24167278 | Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression. |
| 531 | 24167278 | GATA-binding protein 3 (Gata3) controls the differentiation of naive CD4 T cells into T helper 2 (Th2) cells by induction of chromatin remodeling of the Th2 cytokine gene loci, direct transactivation of Il5 and Il13 genes, and inhibition of Ifng. |
| 532 | 24167278 | We herein found that Gata3 associates with RuvB-like protein 2 (Ruvbl2) and represses the expression of a CDK inhibitor, cyclin-dependent kinase inhibitor 2c (Cdkn2c) to facilitate the proliferation of Th2 cells. |
| 533 | 24167278 | Gata3 directly bound to the Cdkn2c locus in an Ruvbl2-dependent manner. |
| 534 | 24167278 | We therefore have identified a functional Gata3/Ruvbl2 complex that regulates the proliferation of differentiating Th2 cells through the repression of a CDK inhibitor, Cdkn2c. |
| 535 | 24204280 | Moreover, we revealed that the presentation of HLA-DQβ enhanced by LANA knockdown did not help LANA-specific CD4+ T cell recognition of PEL cells, and the inhibition of CIITA by LANA is independent of IL-4 or IFN-γ signaling but dependent on the direct interaction of LANA with IRF-4 (an activator of both the pIII and pIV CIITA promoters). |
| 536 | 24204576 | Samples were analysed by immunofluorescence to identify the presence and abundance of B-B7 (B-cells), CD4 (LTh), CD8 (LTc), γδT cell receptor (TCR) and CD335/NKp46 (NK cells) -positive immune cells. |
| 537 | 24204576 | Quantitative real time PCR (QPCR) was carried out to analyse mRNA relative abundance of FOXP3 (a marker of regulatory T (Treg) cells) and a panel of immune factors, including MHC-I, LIF, Interleukins 1, 2, 6, 8, 10, 11,12A, IFNa and IFNG. |
| 538 | 24204576 | Results indicate that B-B7+ cells are quite populous in bovine endometrial tissue, CD4+ and CD8+ -cells are present in moderate numbers and γδTCR+ and CD335+ cells are present in low numbers. |
| 539 | 24204576 | Neither B lymphocytes nor T lymphocyte subsets were regulated temporally during the oestrous cycle or by pregnancy prior to implantation. mRNA transcript abundance of the immune factors LIF, IL1b, IL8 and IL12A, IFNa and IFNG, expression was regulated temporally during the estrous cycle and LIF, IL1b, IL-10, IL11, IL12A were also temporally regulated during pregnancy. |
| 540 | 24204576 | Samples were analysed by immunofluorescence to identify the presence and abundance of B-B7 (B-cells), CD4 (LTh), CD8 (LTc), γδT cell receptor (TCR) and CD335/NKp46 (NK cells) -positive immune cells. |
| 541 | 24204576 | Quantitative real time PCR (QPCR) was carried out to analyse mRNA relative abundance of FOXP3 (a marker of regulatory T (Treg) cells) and a panel of immune factors, including MHC-I, LIF, Interleukins 1, 2, 6, 8, 10, 11,12A, IFNa and IFNG. |
| 542 | 24204576 | Results indicate that B-B7+ cells are quite populous in bovine endometrial tissue, CD4+ and CD8+ -cells are present in moderate numbers and γδTCR+ and CD335+ cells are present in low numbers. |
| 543 | 24204576 | Neither B lymphocytes nor T lymphocyte subsets were regulated temporally during the oestrous cycle or by pregnancy prior to implantation. mRNA transcript abundance of the immune factors LIF, IL1b, IL8 and IL12A, IFNa and IFNG, expression was regulated temporally during the estrous cycle and LIF, IL1b, IL-10, IL11, IL12A were also temporally regulated during pregnancy. |
| 544 | 24216234 | Rosette pre-depletion of blood was also investigated for detecting CD4+ or CD8+ T-cell responses using the IFN-g ELISPOT assay. |
| 545 | 24216234 | Rosette pre-depletion of whole blood proved to be effective in detecting CD4+ or CD8+ T-cell responses similarly to flow cytometry. |
| 546 | 24216234 | Taken together, the following recommendations are suggested to optimize the CMV-ELISPOT for transplantation settings: (1) use PMA/iono as positive control; (2) whole virus particle should be used to avoid peptide-related false negative responses; (3) a rosette pre-depletion step may be useful to detect CD4+ or CD8+ T-cell responses. |
| 547 | 24216234 | Rosette pre-depletion of blood was also investigated for detecting CD4+ or CD8+ T-cell responses using the IFN-g ELISPOT assay. |
| 548 | 24216234 | Rosette pre-depletion of whole blood proved to be effective in detecting CD4+ or CD8+ T-cell responses similarly to flow cytometry. |
| 549 | 24216234 | Taken together, the following recommendations are suggested to optimize the CMV-ELISPOT for transplantation settings: (1) use PMA/iono as positive control; (2) whole virus particle should be used to avoid peptide-related false negative responses; (3) a rosette pre-depletion step may be useful to detect CD4+ or CD8+ T-cell responses. |
| 550 | 24216234 | Rosette pre-depletion of blood was also investigated for detecting CD4+ or CD8+ T-cell responses using the IFN-g ELISPOT assay. |
| 551 | 24216234 | Rosette pre-depletion of whole blood proved to be effective in detecting CD4+ or CD8+ T-cell responses similarly to flow cytometry. |
| 552 | 24216234 | Taken together, the following recommendations are suggested to optimize the CMV-ELISPOT for transplantation settings: (1) use PMA/iono as positive control; (2) whole virus particle should be used to avoid peptide-related false negative responses; (3) a rosette pre-depletion step may be useful to detect CD4+ or CD8+ T-cell responses. |
| 553 | 24244422 | Downregulation of IFNG in CD4(+) T cells in lung cancer through hypermethylation: a possible mechanism of tumor-induced immunosuppression. |
| 554 | 24244422 | Hypermethylation of the IFNG promoter in CD4(+) T cells and plasma IFNG was negatively correlated. |
| 555 | 24244422 | CD4(+) T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. |
| 556 | 24244422 | In conclusion, decreased IFNG expression of CD4(+) T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. |
| 557 | 24244422 | Our study suggests that interaction between lung cancer cells and CD4(+) T cells induces DNMT expression and IFNG promoter hypermethylation in CD4(+) T cell, which may serve as an important mechanism of tumor-induced immunosuppression. |
| 558 | 24244422 | Downregulation of IFNG in CD4(+) T cells in lung cancer through hypermethylation: a possible mechanism of tumor-induced immunosuppression. |
| 559 | 24244422 | Hypermethylation of the IFNG promoter in CD4(+) T cells and plasma IFNG was negatively correlated. |
| 560 | 24244422 | CD4(+) T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. |
| 561 | 24244422 | In conclusion, decreased IFNG expression of CD4(+) T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. |
| 562 | 24244422 | Our study suggests that interaction between lung cancer cells and CD4(+) T cells induces DNMT expression and IFNG promoter hypermethylation in CD4(+) T cell, which may serve as an important mechanism of tumor-induced immunosuppression. |
| 563 | 24244422 | Downregulation of IFNG in CD4(+) T cells in lung cancer through hypermethylation: a possible mechanism of tumor-induced immunosuppression. |
| 564 | 24244422 | Hypermethylation of the IFNG promoter in CD4(+) T cells and plasma IFNG was negatively correlated. |
| 565 | 24244422 | CD4(+) T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. |
| 566 | 24244422 | In conclusion, decreased IFNG expression of CD4(+) T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. |
| 567 | 24244422 | Our study suggests that interaction between lung cancer cells and CD4(+) T cells induces DNMT expression and IFNG promoter hypermethylation in CD4(+) T cell, which may serve as an important mechanism of tumor-induced immunosuppression. |
| 568 | 24244422 | Downregulation of IFNG in CD4(+) T cells in lung cancer through hypermethylation: a possible mechanism of tumor-induced immunosuppression. |
| 569 | 24244422 | Hypermethylation of the IFNG promoter in CD4(+) T cells and plasma IFNG was negatively correlated. |
| 570 | 24244422 | CD4(+) T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. |
| 571 | 24244422 | In conclusion, decreased IFNG expression of CD4(+) T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. |
| 572 | 24244422 | Our study suggests that interaction between lung cancer cells and CD4(+) T cells induces DNMT expression and IFNG promoter hypermethylation in CD4(+) T cell, which may serve as an important mechanism of tumor-induced immunosuppression. |
| 573 | 24244422 | Downregulation of IFNG in CD4(+) T cells in lung cancer through hypermethylation: a possible mechanism of tumor-induced immunosuppression. |
| 574 | 24244422 | Hypermethylation of the IFNG promoter in CD4(+) T cells and plasma IFNG was negatively correlated. |
| 575 | 24244422 | CD4(+) T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. |
| 576 | 24244422 | In conclusion, decreased IFNG expression of CD4(+) T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. |
| 577 | 24244422 | Our study suggests that interaction between lung cancer cells and CD4(+) T cells induces DNMT expression and IFNG promoter hypermethylation in CD4(+) T cell, which may serve as an important mechanism of tumor-induced immunosuppression. |
| 578 | 24249741 | SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells. |
| 579 | 24249741 | Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. |
| 580 | 24249741 | Both γδ and αβ(+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. |
| 581 | 24249741 | In addition to the lung, IL-17A(+) γδ and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal αβ and γδ T cell development in the thymus. |
| 582 | 24249741 | Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4(+) and Vγ6/Vδ1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. |
| 583 | 24249741 | Given that serpinb1a is preferentially expressed in WT IL-17A(+) γδ and CD4(+) Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype. |
| 584 | 24249741 | SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells. |
| 585 | 24249741 | Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. |
| 586 | 24249741 | Both γδ and αβ(+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. |
| 587 | 24249741 | In addition to the lung, IL-17A(+) γδ and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal αβ and γδ T cell development in the thymus. |
| 588 | 24249741 | Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4(+) and Vγ6/Vδ1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. |
| 589 | 24249741 | Given that serpinb1a is preferentially expressed in WT IL-17A(+) γδ and CD4(+) Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype. |
| 590 | 24249741 | SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells. |
| 591 | 24249741 | Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. |
| 592 | 24249741 | Both γδ and αβ(+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. |
| 593 | 24249741 | In addition to the lung, IL-17A(+) γδ and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal αβ and γδ T cell development in the thymus. |
| 594 | 24249741 | Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4(+) and Vγ6/Vδ1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. |
| 595 | 24249741 | Given that serpinb1a is preferentially expressed in WT IL-17A(+) γδ and CD4(+) Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype. |
| 596 | 24249741 | SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells. |
| 597 | 24249741 | Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. |
| 598 | 24249741 | Both γδ and αβ(+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. |
| 599 | 24249741 | In addition to the lung, IL-17A(+) γδ and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal αβ and γδ T cell development in the thymus. |
| 600 | 24249741 | Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4(+) and Vγ6/Vδ1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. |
| 601 | 24249741 | Given that serpinb1a is preferentially expressed in WT IL-17A(+) γδ and CD4(+) Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype. |
| 602 | 24249741 | SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells. |
| 603 | 24249741 | Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. |
| 604 | 24249741 | Both γδ and αβ(+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. |
| 605 | 24249741 | In addition to the lung, IL-17A(+) γδ and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal αβ and γδ T cell development in the thymus. |
| 606 | 24249741 | Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4(+) and Vγ6/Vδ1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. |
| 607 | 24249741 | Given that serpinb1a is preferentially expressed in WT IL-17A(+) γδ and CD4(+) Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype. |
| 608 | 24266365 | The present review focuses on a small subset of iTregs that produces IFNg, comprises only 0.04% of all CD4(+) T lymphocytes in the blood of healthy individuals, and increases strongly during an immune response. |
| 609 | 24266365 | IFNg(+) Tregs are induced by IFNg and IL12, making them sensors for inflammatory cytokines. |
| 610 | 24296812 | TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of T-box transcription factors T-bet with graded loss of Eomesodermin (Eomes) expression (T-bet(Hi)Eomes(Hi/Lo)) when compared with TNF-α(+) CD4(+) T cells expressing lower levels of both T-bet and Eomes (T-bet(-)Eomes(-)). |
| 611 | 24296812 | Furthermore, TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of perforin and interleukin (IL)-2 and displayed a terminally differentiated phenotype (CCR7(-)CD27(-)CD45RA(-)CD57(+)CD62L(-)). |
| 612 | 24296812 | In contrast, TNF-α(+) alone CMV-specific CD4(+) T cells were predominantly early-memory phenotype with a proportion of these cells displaying T memory stem-cell phenotype (CD95(+)CD45RA(+)CCR7(+)CD27(+)). |
| 613 | 24296812 | In vitro stimulation of CMV-specific CD4(+) T cells with viral antigen in the presence of IL-12 was sufficient to dramatically change the transcriptional and functional profile of TNF-α(+) CD4(+) T cells, whereas TNF-α(+) and IFN-γ(+) CD4(+) T cells remained unaltered. |
| 614 | 24296812 | TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of T-box transcription factors T-bet with graded loss of Eomesodermin (Eomes) expression (T-bet(Hi)Eomes(Hi/Lo)) when compared with TNF-α(+) CD4(+) T cells expressing lower levels of both T-bet and Eomes (T-bet(-)Eomes(-)). |
| 615 | 24296812 | Furthermore, TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of perforin and interleukin (IL)-2 and displayed a terminally differentiated phenotype (CCR7(-)CD27(-)CD45RA(-)CD57(+)CD62L(-)). |
| 616 | 24296812 | In contrast, TNF-α(+) alone CMV-specific CD4(+) T cells were predominantly early-memory phenotype with a proportion of these cells displaying T memory stem-cell phenotype (CD95(+)CD45RA(+)CCR7(+)CD27(+)). |
| 617 | 24296812 | In vitro stimulation of CMV-specific CD4(+) T cells with viral antigen in the presence of IL-12 was sufficient to dramatically change the transcriptional and functional profile of TNF-α(+) CD4(+) T cells, whereas TNF-α(+) and IFN-γ(+) CD4(+) T cells remained unaltered. |
| 618 | 24296812 | TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of T-box transcription factors T-bet with graded loss of Eomesodermin (Eomes) expression (T-bet(Hi)Eomes(Hi/Lo)) when compared with TNF-α(+) CD4(+) T cells expressing lower levels of both T-bet and Eomes (T-bet(-)Eomes(-)). |
| 619 | 24296812 | Furthermore, TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of perforin and interleukin (IL)-2 and displayed a terminally differentiated phenotype (CCR7(-)CD27(-)CD45RA(-)CD57(+)CD62L(-)). |
| 620 | 24296812 | In contrast, TNF-α(+) alone CMV-specific CD4(+) T cells were predominantly early-memory phenotype with a proportion of these cells displaying T memory stem-cell phenotype (CD95(+)CD45RA(+)CCR7(+)CD27(+)). |
| 621 | 24296812 | In vitro stimulation of CMV-specific CD4(+) T cells with viral antigen in the presence of IL-12 was sufficient to dramatically change the transcriptional and functional profile of TNF-α(+) CD4(+) T cells, whereas TNF-α(+) and IFN-γ(+) CD4(+) T cells remained unaltered. |
| 622 | 24296812 | TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of T-box transcription factors T-bet with graded loss of Eomesodermin (Eomes) expression (T-bet(Hi)Eomes(Hi/Lo)) when compared with TNF-α(+) CD4(+) T cells expressing lower levels of both T-bet and Eomes (T-bet(-)Eomes(-)). |
| 623 | 24296812 | Furthermore, TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of perforin and interleukin (IL)-2 and displayed a terminally differentiated phenotype (CCR7(-)CD27(-)CD45RA(-)CD57(+)CD62L(-)). |
| 624 | 24296812 | In contrast, TNF-α(+) alone CMV-specific CD4(+) T cells were predominantly early-memory phenotype with a proportion of these cells displaying T memory stem-cell phenotype (CD95(+)CD45RA(+)CCR7(+)CD27(+)). |
| 625 | 24296812 | In vitro stimulation of CMV-specific CD4(+) T cells with viral antigen in the presence of IL-12 was sufficient to dramatically change the transcriptional and functional profile of TNF-α(+) CD4(+) T cells, whereas TNF-α(+) and IFN-γ(+) CD4(+) T cells remained unaltered. |
| 626 | 24313359 | Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics. |
| 627 | 24313359 | Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. |
| 628 | 24313359 | In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. |
| 629 | 24313359 | Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. |
| 630 | 24313359 | Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. |
| 631 | 24313359 | CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. |
| 632 | 24313359 | While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. |
| 633 | 24313359 | CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population. |
| 634 | 24313359 | Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics. |
| 635 | 24313359 | Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. |
| 636 | 24313359 | In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. |
| 637 | 24313359 | Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. |
| 638 | 24313359 | Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. |
| 639 | 24313359 | CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. |
| 640 | 24313359 | While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. |
| 641 | 24313359 | CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population. |
| 642 | 24313359 | Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics. |
| 643 | 24313359 | Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. |
| 644 | 24313359 | In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. |
| 645 | 24313359 | Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. |
| 646 | 24313359 | Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. |
| 647 | 24313359 | CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. |
| 648 | 24313359 | While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. |
| 649 | 24313359 | CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population. |
| 650 | 24313359 | Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics. |
| 651 | 24313359 | Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. |
| 652 | 24313359 | In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. |
| 653 | 24313359 | Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. |
| 654 | 24313359 | Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. |
| 655 | 24313359 | CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. |
| 656 | 24313359 | While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. |
| 657 | 24313359 | CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population. |
| 658 | 24313359 | Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics. |
| 659 | 24313359 | Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. |
| 660 | 24313359 | In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. |
| 661 | 24313359 | Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. |
| 662 | 24313359 | Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. |
| 663 | 24313359 | CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. |
| 664 | 24313359 | While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. |
| 665 | 24313359 | CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population. |
| 666 | 24313359 | Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics. |
| 667 | 24313359 | Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. |
| 668 | 24313359 | In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. |
| 669 | 24313359 | Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. |
| 670 | 24313359 | Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. |
| 671 | 24313359 | CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. |
| 672 | 24313359 | While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. |
| 673 | 24313359 | CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population. |
| 674 | 24313359 | Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics. |
| 675 | 24313359 | Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. |
| 676 | 24313359 | In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. |
| 677 | 24313359 | Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. |
| 678 | 24313359 | Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. |
| 679 | 24313359 | CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. |
| 680 | 24313359 | While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. |
| 681 | 24313359 | CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population. |
| 682 | 24313359 | Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics. |
| 683 | 24313359 | Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. |
| 684 | 24313359 | In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. |
| 685 | 24313359 | Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. |
| 686 | 24313359 | Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. |
| 687 | 24313359 | CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. |
| 688 | 24313359 | While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. |
| 689 | 24313359 | CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population. |