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Gene Information

Gene symbol: FOXP3

Gene name: forkhead box P3

HGNC ID: 6106

Synonyms: JM2, XPID, AIID, PIDX, DIETER, SCURFIN

Related Genes

# Gene Symbol Number of hits
1 ADA 1 hits
2 AIRE 1 hits
3 AKT1 1 hits
4 APOE 1 hits
5 BCL6 1 hits
6 BTK 1 hits
7 C5AR1 1 hits
8 CALR 1 hits
9 CCRN4L 1 hits
10 CD19 1 hits
11 CD207 1 hits
12 CD274 1 hits
13 CD38 1 hits
14 CD4 1 hits
15 CD40 1 hits
16 CD40LG 1 hits
17 CD44 1 hits
18 CD80 1 hits
19 CD86 1 hits
20 CD8A 1 hits
21 CD9 1 hits
22 CEBPB 1 hits
23 CELIAC3 1 hits
24 CRLF2 1 hits
25 CSF2 1 hits
26 CTLA4 1 hits
27 CXCL10 1 hits
28 CXCL3 1 hits
29 CXCL9 1 hits
30 CXCR5 1 hits
31 DKK1 1 hits
32 EBI3 1 hits
33 ENTPD1 1 hits
34 EPS8 1 hits
35 ERBB2 1 hits
36 FAS 1 hits
37 FCGR3A 1 hits
38 FOXP2 1 hits
39 GAD2 1 hits
40 GATA3 1 hits
41 GDF15 1 hits
42 GZMB 1 hits
43 HBEGF 1 hits
44 HLA-A 1 hits
45 HLA-E 1 hits
46 HLA-G 1 hits
47 HSP90B1 1 hits
48 HSPA1A 1 hits
49 ICOS 1 hits
50 IFNG 1 hits
51 IKZF2 1 hits
52 IL10 1 hits
53 IL12A 1 hits
54 IL17A 1 hits
55 IL17D 1 hits
56 IL18 1 hits
57 IL1B 1 hits
58 IL2 1 hits
59 IL28B 1 hits
60 IL2RA 1 hits
61 IL4 1 hits
62 IL4R 1 hits
63 IL5 1 hits
64 IL6 1 hits
65 IL7R 1 hits
66 IL8 1 hits
67 INDO 1 hits
68 INS 1 hits
69 ISG20 1 hits
70 ITGAE 1 hits
71 ITGAM 1 hits
72 LBR 1 hits
73 LMNA 1 hits
74 LTA 1 hits
75 MRC1 1 hits
76 MUC1 1 hits
77 MUC16 1 hits
78 MUC6 1 hits
79 NCAM1 1 hits
80 PDCD1 1 hits
81 PECAM1 1 hits
82 PIK3CA 1 hits
83 POLE3 1 hits
84 RAB33A 1 hits
85 RARA 1 hits
86 RPE 1 hits
87 SEC14L1 1 hits
88 SELL 1 hits
89 SLA 1 hits
90 SLC10A3 1 hits
91 SNORD14A 1 hits
92 SPINT1 1 hits
93 STAT5A 1 hits
94 TBX21 1 hits
95 TFRC 1 hits
96 TGFA 1 hits
97 TGFB1 1 hits
98 TH1L 1 hits
99 TLR2 1 hits
100 TLR4 1 hits
101 TNF 1 hits
102 TNFRSF18 1 hits
103 TNFRSF1A 1 hits
104 TNFRSF4 1 hits
105 TSC22D3 1 hits
106 TSLP 1 hits
107 ZP3 1 hits

Related Sentences

# PMID Sentence
1 15611232 Type I IFN negatively regulates CD8+ T cell responses through IL-10-producing CD4+ T regulatory 1 cells.
2 15611232 We used vaccine-induced, antiviral CD8(+) T cell responses in IFN-beta (IFN-beta(-/-))- or type I IFN receptor (IFNAR(-/-))-deficient mice to study immunomodulating effects of type I IFN that are not complicated by the interference of a concomitant virus infection.
3 15611232 Compared with normal B6 mice, IFNAR(-/-) or IFN-beta(-/-) mice have normal numbers of CD4(+) and CD8(+) T cells, and CD25(+)FoxP3(+) T regulatory (T(R)) cells in liver and spleen.
4 15611232 IFN-gamma and TNF-alpha production and clonal expansion of specific CD8(+) T cells from normal and knockout mice are similar.
5 15611232 CD25(+)FoxP3(+) T(R) cells down-modulate vaccine-primed CD8(+) T cell responses in normal, IFNAR(-/-), or IFN-beta(-/-) mice to a comparable extent.
6 15611232 Low IFN-alpha or IFN-beta doses (500-10(3) U/mouse) down-modulate CD8(+) T cells priming in vivo.
7 15611232 IFNAR- and IFN-beta-deficient mice generate 2- to 3-fold lower numbers of IL-10-producing CD4(+) T cells after polyclonal or specific stimulation in vitro or in vivo.
8 15611232 CD8(+) T cell responses are thus subjected to negative control by both CD25(+)FoxP3(+) T(R) cells and CD4(+)IL-10(+) T(R1) cells, but only development of the latter T(R) cells depends on type I IFN.
9 15735048 CD4(+) Treg cells do not secrete interleukin (IL)-10 and transforming growth factor beta cytokines but express CD25, the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), and Forkhead Box P3 (Foxp3), and are capable of suppressing the proliferative responses of naive CD4(+) and CD8(+) T cells to stimulation with mitogenic anti-CD3 antibody.
10 15735048 Importantly, these Treg cells suppress IL-2 secretion by CD4(+) effector T cells specific for either EBNA1 or a melanoma antigen, suggesting that these CD4(+) Treg cells induce immune suppression.
11 16446177 Lately, the existence of subpopulations of regulatory T lymphocytes (RTL) able to limit the immune response in a specific form has been established, specially inhibiting the proliferation and activity of CD4+ and CD8+ effector T lymphocytes.
12 16446177 These cellular subpopulations, mostly CD4+/CD25+/Foxp3+ T lymphocytes (Treg) of thymic origin, or TR1 lymphocytes able to release IL-10, and tumour growth factor beta (TGF-beta) producing TH3 lymphocytes, would be accumulated in the body during tumour growth, inhibiting the immune response.
13 16461790 An induction of FoxP3 mRNA expression in some mycobacteria-stimulated whole-blood samples is also being found, which suggests the presence of BCG-induced regulatory CD4 T cells.
14 16461790 Finally, stimulation of whole blood with mycobacterial antigens has resulted in a consistent pattern of cytokine release: significant numbers of infants make either large amounts of the effector cytokine interferon-gamma, or large amounts of the regulatory cytokine interleukin-10, but not both.
15 16461790 Tests will, therefore, be made to determine whether CD8 or regulatory CD4 T-cell responses, as well as "outlier" cytokine responses, are associated with vaccination-induced protection against tuberculosis.
16 16468035 The ascites fluid contained the chemokines CCL10, CCL15, and CCL18 which was associated with a large influx of activated T cells, including CD8(+) T cells recognizing HLA-A2 tetramer complexes with peptides from Melan-A and NA17-A.
17 16468035 Although these defects were T cell intrinsic, we also observed abundant CD4(+)CD25(+)FoxP3(+) T cells, as well as transcripts for FoxP3, IL-10, PD-L1/B7-H1, and indoleamine-2,3-dioxygenase (IDO).
18 16478885 Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C.
19 16478885 CD4(+)CD25(+) T cells have been implicated in HCV persistence because their frequency is increased in the blood of HCV-infected patients and their in vitro depletion results in increased IFN-gamma production by HCV-specific T cells.
20 16478885 Studying a well-characterized cohort of 16 chimpanzees, the sole animal model for HCV infection, we here demonstrate that the frequency of Foxp3(+)CD4(+)CD25(+) regulatory T cells (T(Regs)) and the extent of suppression was as high in spontaneously HCV-recovered chimpanzees as in persistently HCV-infected chimpanzees.
21 16478885 Foxp3(+)CD4(+)CD25(+) T(Regs) suppressed IFN-gamma production, expansion, and activation-induced cell death of HCV-specific T cells after recovery from HCV infection and in persistent HCV infection.
22 16478885 However, Foxp3(+)CD4(+)CD25(+) T(Reg) cells of both HCV-recovered and HCV-infected chimpanzees differed from Foxp3(+)CD4(+)CD25(+)T(Reg) cells of HCV-naive chimpanzees in increased IL-2 responsiveness and lower T-cell receptor excision circle content, implying a history of in vivo proliferation.
23 16478885 This result suggests that HCV infection alters the population of Foxp3(+)CD4(+)CD25(+) T(Reg) cells.
24 16478885 Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C.
25 16478885 CD4(+)CD25(+) T cells have been implicated in HCV persistence because their frequency is increased in the blood of HCV-infected patients and their in vitro depletion results in increased IFN-gamma production by HCV-specific T cells.
26 16478885 Studying a well-characterized cohort of 16 chimpanzees, the sole animal model for HCV infection, we here demonstrate that the frequency of Foxp3(+)CD4(+)CD25(+) regulatory T cells (T(Regs)) and the extent of suppression was as high in spontaneously HCV-recovered chimpanzees as in persistently HCV-infected chimpanzees.
27 16478885 Foxp3(+)CD4(+)CD25(+) T(Regs) suppressed IFN-gamma production, expansion, and activation-induced cell death of HCV-specific T cells after recovery from HCV infection and in persistent HCV infection.
28 16478885 However, Foxp3(+)CD4(+)CD25(+) T(Reg) cells of both HCV-recovered and HCV-infected chimpanzees differed from Foxp3(+)CD4(+)CD25(+)T(Reg) cells of HCV-naive chimpanzees in increased IL-2 responsiveness and lower T-cell receptor excision circle content, implying a history of in vivo proliferation.
29 16478885 This result suggests that HCV infection alters the population of Foxp3(+)CD4(+)CD25(+) T(Reg) cells.
30 16478885 Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C.
31 16478885 CD4(+)CD25(+) T cells have been implicated in HCV persistence because their frequency is increased in the blood of HCV-infected patients and their in vitro depletion results in increased IFN-gamma production by HCV-specific T cells.
32 16478885 Studying a well-characterized cohort of 16 chimpanzees, the sole animal model for HCV infection, we here demonstrate that the frequency of Foxp3(+)CD4(+)CD25(+) regulatory T cells (T(Regs)) and the extent of suppression was as high in spontaneously HCV-recovered chimpanzees as in persistently HCV-infected chimpanzees.
33 16478885 Foxp3(+)CD4(+)CD25(+) T(Regs) suppressed IFN-gamma production, expansion, and activation-induced cell death of HCV-specific T cells after recovery from HCV infection and in persistent HCV infection.
34 16478885 However, Foxp3(+)CD4(+)CD25(+) T(Reg) cells of both HCV-recovered and HCV-infected chimpanzees differed from Foxp3(+)CD4(+)CD25(+)T(Reg) cells of HCV-naive chimpanzees in increased IL-2 responsiveness and lower T-cell receptor excision circle content, implying a history of in vivo proliferation.
35 16478885 This result suggests that HCV infection alters the population of Foxp3(+)CD4(+)CD25(+) T(Reg) cells.
36 16478885 Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C.
37 16478885 CD4(+)CD25(+) T cells have been implicated in HCV persistence because their frequency is increased in the blood of HCV-infected patients and their in vitro depletion results in increased IFN-gamma production by HCV-specific T cells.
38 16478885 Studying a well-characterized cohort of 16 chimpanzees, the sole animal model for HCV infection, we here demonstrate that the frequency of Foxp3(+)CD4(+)CD25(+) regulatory T cells (T(Regs)) and the extent of suppression was as high in spontaneously HCV-recovered chimpanzees as in persistently HCV-infected chimpanzees.
39 16478885 Foxp3(+)CD4(+)CD25(+) T(Regs) suppressed IFN-gamma production, expansion, and activation-induced cell death of HCV-specific T cells after recovery from HCV infection and in persistent HCV infection.
40 16478885 However, Foxp3(+)CD4(+)CD25(+) T(Reg) cells of both HCV-recovered and HCV-infected chimpanzees differed from Foxp3(+)CD4(+)CD25(+)T(Reg) cells of HCV-naive chimpanzees in increased IL-2 responsiveness and lower T-cell receptor excision circle content, implying a history of in vivo proliferation.
41 16478885 This result suggests that HCV infection alters the population of Foxp3(+)CD4(+)CD25(+) T(Reg) cells.
42 16478885 Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C.
43 16478885 CD4(+)CD25(+) T cells have been implicated in HCV persistence because their frequency is increased in the blood of HCV-infected patients and their in vitro depletion results in increased IFN-gamma production by HCV-specific T cells.
44 16478885 Studying a well-characterized cohort of 16 chimpanzees, the sole animal model for HCV infection, we here demonstrate that the frequency of Foxp3(+)CD4(+)CD25(+) regulatory T cells (T(Regs)) and the extent of suppression was as high in spontaneously HCV-recovered chimpanzees as in persistently HCV-infected chimpanzees.
45 16478885 Foxp3(+)CD4(+)CD25(+) T(Regs) suppressed IFN-gamma production, expansion, and activation-induced cell death of HCV-specific T cells after recovery from HCV infection and in persistent HCV infection.
46 16478885 However, Foxp3(+)CD4(+)CD25(+) T(Reg) cells of both HCV-recovered and HCV-infected chimpanzees differed from Foxp3(+)CD4(+)CD25(+)T(Reg) cells of HCV-naive chimpanzees in increased IL-2 responsiveness and lower T-cell receptor excision circle content, implying a history of in vivo proliferation.
47 16478885 This result suggests that HCV infection alters the population of Foxp3(+)CD4(+)CD25(+) T(Reg) cells.
48 16493027 Cyclophosphamide could 1) abolish the suppressive function of CD4+CD25+Foxp3+ regulatory T cells, 2) markedly enhance the magnitude of secondary but not primary CTL responses induced by DEX vaccines, 3) synergize with DEX in therapy but not prophylaxis tumor models.
49 16493027 Therefore, therapeutic vaccines such as DEX aimed at boosting tumor-primed effector T cells could benefit procedures that minimize the effects of CD4+CD25+ regulatory T cells.
50 16585551 Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes.
51 16585551 We found that intranasal vaccination of NOD mice with plasmid DNA encoding mouse proinsulin II-induced CD4+ T(reg) that suppressed diabetes development, both after adoptive cotransfer with "diabetogenic" spleen cells and after transfer into NOD mice given cyclophosphamide to accelerate diabetes onset.
52 16585551 In contrast to prototypic CD4+ CD25+ T(reg), CD4+ T(reg) induced by proinsulin DNA were both CD25+ and CD25- and not defined by markers such as glucocorticoid-induced TNFR-related protein (GITR), CD103, or Foxp3.
53 16585551 However, diabetes was prevented when DNA vaccination was performed under the cover of CD40 ligand blockade, known to prevent priming of CTL by mucosal Ag.
54 16778987 CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells.
55 16778987 We examined the mechanisms of action of anti-CTLA4 and a GM-CSF-transduced tumor cell vaccine (Gvax) and their impact on the balance of effector T cells (Teffs) and Tregs in an in vivo model of B16/BL6 melanoma.
56 16778987 Tumor challenge increased the frequency of Tregs in lymph nodes, and untreated tumors became infiltrated by CD4+Foxp3- and CD4+Foxp3+ T cells but few CD8+ T cells.
57 16778987 The data suggest that Tregs control both CD4+ and CD8+ T cell activity within the tumor, highlight the importance of the intratumor ratio of effectors to regulators, and demonstrate inversion of the ratio and correlation with tumor rejection during Gvax/anti-CTLA4 immunotherapy.
58 16790365 However, in this study, we demonstrate protection against disease by covaccination with a mutant B7-1 molecule (B7-1wa) that binds the negative T cell regulator CTLA-4 (CD152), but not CD28.
59 16790365 In vitro, the T cells of covaccinated mice had negative responses to both insulin and GAD65, and this was restored by adding blocking antibodies to transforming growth factor beta1 (TGF-beta1), suggesting a role for this cytokine.
60 16790365 Furthermore, vaccinated mice had increased numbers of T cells with Tr-associated markers, such as CTLA-4, Foxp3, and membrane-bound TGF-beta1.
61 16799332 Docetaxel induced a mild lymphodepletion in mice, both CD4 and CD8 subsets were reduced in LN and spleens.
62 16799332 Interestingly, docetaxel also diminished the number of memory CD8+ T cells (CD122+) and possible CD4+ CD25+ Foxp3+ natural Treg cells.
63 16918694 Sublingual tolerance induction with antigen conjugated to cholera toxin B subunit induces Foxp3+CD25+CD4+ regulatory T cells and suppresses delayed-type hypersensitivity reactions.
64 16918694 -induced tolerance be explained by the generation of Foxp3+CD25+CD4+ regulatory T cells (T(reg))?
65 16918694 The intracellular expression of Foxp3 was strongly increased in OVA-specific (KJ1-26+) CD4+ T cells from OVA/CTB-treated mice.
66 16918694 Thus, s.l. administration of CTB-conjugated Ag can efficiently induce peripheral T-cell tolerance associated with strong increases in serum TGF-beta levels and in Ag-specific Foxp3+CD25+CD4+ T(reg) cells.
67 16918694 Sublingual tolerance induction with antigen conjugated to cholera toxin B subunit induces Foxp3+CD25+CD4+ regulatory T cells and suppresses delayed-type hypersensitivity reactions.
68 16918694 -induced tolerance be explained by the generation of Foxp3+CD25+CD4+ regulatory T cells (T(reg))?
69 16918694 The intracellular expression of Foxp3 was strongly increased in OVA-specific (KJ1-26+) CD4+ T cells from OVA/CTB-treated mice.
70 16918694 Thus, s.l. administration of CTB-conjugated Ag can efficiently induce peripheral T-cell tolerance associated with strong increases in serum TGF-beta levels and in Ag-specific Foxp3+CD25+CD4+ T(reg) cells.
71 16918694 Sublingual tolerance induction with antigen conjugated to cholera toxin B subunit induces Foxp3+CD25+CD4+ regulatory T cells and suppresses delayed-type hypersensitivity reactions.
72 16918694 -induced tolerance be explained by the generation of Foxp3+CD25+CD4+ regulatory T cells (T(reg))?
73 16918694 The intracellular expression of Foxp3 was strongly increased in OVA-specific (KJ1-26+) CD4+ T cells from OVA/CTB-treated mice.
74 16918694 Thus, s.l. administration of CTB-conjugated Ag can efficiently induce peripheral T-cell tolerance associated with strong increases in serum TGF-beta levels and in Ag-specific Foxp3+CD25+CD4+ T(reg) cells.
75 16918694 Sublingual tolerance induction with antigen conjugated to cholera toxin B subunit induces Foxp3+CD25+CD4+ regulatory T cells and suppresses delayed-type hypersensitivity reactions.
76 16918694 -induced tolerance be explained by the generation of Foxp3+CD25+CD4+ regulatory T cells (T(reg))?
77 16918694 The intracellular expression of Foxp3 was strongly increased in OVA-specific (KJ1-26+) CD4+ T cells from OVA/CTB-treated mice.
78 16918694 Thus, s.l. administration of CTB-conjugated Ag can efficiently induce peripheral T-cell tolerance associated with strong increases in serum TGF-beta levels and in Ag-specific Foxp3+CD25+CD4+ T(reg) cells.
79 16934529 CD4(+)CD25(high) FOXP3-expressing regulatory T cells (Treg) can suppress immune responses to infections and tumors, thereby promoting microbial persistence and tumor progression.
80 16934529 We found increased numbers of CD4(+)FOXP3(+) Treg in the tumor compared to tumor-free gastric mucosa.
81 16934529 CD4(+)CD25(high) FOXP3-expressing regulatory T cells (Treg) can suppress immune responses to infections and tumors, thereby promoting microbial persistence and tumor progression.
82 16934529 We found increased numbers of CD4(+)FOXP3(+) Treg in the tumor compared to tumor-free gastric mucosa.
83 17082611 Analysis of pretherapy tumors demonstrated that advanced primary tumors were infiltrated by CD4+ and CD8+ T cells with an effector/memory phenotype and CD4+CD25+Foxp3+ T suppressor cells.
84 17082611 Tumor-associated effector memory CD8+ T cells displayed impaired cytotoxic function, whereas CD4+CD25+Foxp3+ cells effectively inhibited T cell proliferation demonstrating functional integrity.
85 17082611 IL-12/GM-CSF treatment promoted a rapid up-regulation of CD43 and CD69 on CD8+ effector/memory T cells, augmented their ability to produce IFN-gamma, and restored granzyme B expression.
86 17082611 Both CD8+ T cell activation and T suppressor cell purge were mediated primarily by IL-12 and required IFN-gamma.
87 17082611 Analysis of pretherapy tumors demonstrated that advanced primary tumors were infiltrated by CD4+ and CD8+ T cells with an effector/memory phenotype and CD4+CD25+Foxp3+ T suppressor cells.
88 17082611 Tumor-associated effector memory CD8+ T cells displayed impaired cytotoxic function, whereas CD4+CD25+Foxp3+ cells effectively inhibited T cell proliferation demonstrating functional integrity.
89 17082611 IL-12/GM-CSF treatment promoted a rapid up-regulation of CD43 and CD69 on CD8+ effector/memory T cells, augmented their ability to produce IFN-gamma, and restored granzyme B expression.
90 17082611 Both CD8+ T cell activation and T suppressor cell purge were mediated primarily by IL-12 and required IFN-gamma.
91 17109471 The addition of CpG to the live vaccine resulted in early activation of dermal dendritic cells and increased IL-6 production, as well as in a reduction in the accumulation of Foxp3(+)CD4(+)CD25(+) regulatory T (T(reg)) cells that naturally occurs in the skin following Leishmania infection.
92 17114433 Oral tolerance induction with antigen conjugated to cholera toxin B subunit generates both Foxp3+CD25+ and Foxp3-CD25- CD4+ regulatory T cells.
93 17114433 We investigated the extent to which this oral tolerance is mediated by CD25+CD4+ regulatory T cells (T(reg)).
94 17114433 Foxp3 was strongly expressed by CD25+ T(reg) from OVA/CTB-treated mice, and treatment also markedly expanded CD25+Foxp3+ T(reg).
95 17114433 Our results demonstrate that oral tolerance induced by CTB-conjugated Ag is associated with increase in TGF-beta and in both the frequency and suppressive capacity of Foxp3+ and CTLA-4+ CD25+ T(reg) together with the generation of both Foxp3+ and Foxp3-CD25- CD4+ T(reg).
96 17114433 Oral tolerance induction with antigen conjugated to cholera toxin B subunit generates both Foxp3+CD25+ and Foxp3-CD25- CD4+ regulatory T cells.
97 17114433 We investigated the extent to which this oral tolerance is mediated by CD25+CD4+ regulatory T cells (T(reg)).
98 17114433 Foxp3 was strongly expressed by CD25+ T(reg) from OVA/CTB-treated mice, and treatment also markedly expanded CD25+Foxp3+ T(reg).
99 17114433 Our results demonstrate that oral tolerance induced by CTB-conjugated Ag is associated with increase in TGF-beta and in both the frequency and suppressive capacity of Foxp3+ and CTLA-4+ CD25+ T(reg) together with the generation of both Foxp3+ and Foxp3-CD25- CD4+ T(reg).
100 17114433 Oral tolerance induction with antigen conjugated to cholera toxin B subunit generates both Foxp3+CD25+ and Foxp3-CD25- CD4+ regulatory T cells.
101 17114433 We investigated the extent to which this oral tolerance is mediated by CD25+CD4+ regulatory T cells (T(reg)).
102 17114433 Foxp3 was strongly expressed by CD25+ T(reg) from OVA/CTB-treated mice, and treatment also markedly expanded CD25+Foxp3+ T(reg).
103 17114433 Our results demonstrate that oral tolerance induced by CTB-conjugated Ag is associated with increase in TGF-beta and in both the frequency and suppressive capacity of Foxp3+ and CTLA-4+ CD25+ T(reg) together with the generation of both Foxp3+ and Foxp3-CD25- CD4+ T(reg).
104 17142726 Functional adaptive CD4 Foxp3 T cells develop in MHC class II-deficient mice.
105 17142726 CD4 Foxp3 regulatory T (T(R)) cells are well-defined regulator T cells known to develop in the thymus through positive selection by medium-to-high affinity TCR-MHC interactions.
106 17142726 CD4 Foxp3 T(R) cells are found in secondary lymphoid tissues (spleen and lymph nodes) and peripheral tissues (liver) but not the thymus of severely MHC class II-deficient (Aalpha(-/-) B6) mice.
107 17142726 Furthermore, these T(R) cells suppress IL-2 release and proliferative responses in vitro of naive CD25(-) (CD4 or CD8) T cells from normal B6 mice primed by bead-coupled anti-CD3/anti-CD28 Ab as efficiently as CD4CD25(high) T(R) cells from congenic, normal B6 mice.
108 17142726 MHC class II-independent CD4 Foxp3(+) T(R) cells thus preferentially express the (TGF-beta-induced) integrin molecule alpha(E) (CD103), are generated mainly in the periphery and efficiently mediate immunosuppressive effects.
109 17142726 Functional adaptive CD4 Foxp3 T cells develop in MHC class II-deficient mice.
110 17142726 CD4 Foxp3 regulatory T (T(R)) cells are well-defined regulator T cells known to develop in the thymus through positive selection by medium-to-high affinity TCR-MHC interactions.
111 17142726 CD4 Foxp3 T(R) cells are found in secondary lymphoid tissues (spleen and lymph nodes) and peripheral tissues (liver) but not the thymus of severely MHC class II-deficient (Aalpha(-/-) B6) mice.
112 17142726 Furthermore, these T(R) cells suppress IL-2 release and proliferative responses in vitro of naive CD25(-) (CD4 or CD8) T cells from normal B6 mice primed by bead-coupled anti-CD3/anti-CD28 Ab as efficiently as CD4CD25(high) T(R) cells from congenic, normal B6 mice.
113 17142726 MHC class II-independent CD4 Foxp3(+) T(R) cells thus preferentially express the (TGF-beta-induced) integrin molecule alpha(E) (CD103), are generated mainly in the periphery and efficiently mediate immunosuppressive effects.
114 17142726 Functional adaptive CD4 Foxp3 T cells develop in MHC class II-deficient mice.
115 17142726 CD4 Foxp3 regulatory T (T(R)) cells are well-defined regulator T cells known to develop in the thymus through positive selection by medium-to-high affinity TCR-MHC interactions.
116 17142726 CD4 Foxp3 T(R) cells are found in secondary lymphoid tissues (spleen and lymph nodes) and peripheral tissues (liver) but not the thymus of severely MHC class II-deficient (Aalpha(-/-) B6) mice.
117 17142726 Furthermore, these T(R) cells suppress IL-2 release and proliferative responses in vitro of naive CD25(-) (CD4 or CD8) T cells from normal B6 mice primed by bead-coupled anti-CD3/anti-CD28 Ab as efficiently as CD4CD25(high) T(R) cells from congenic, normal B6 mice.
118 17142726 MHC class II-independent CD4 Foxp3(+) T(R) cells thus preferentially express the (TGF-beta-induced) integrin molecule alpha(E) (CD103), are generated mainly in the periphery and efficiently mediate immunosuppressive effects.
119 17142726 Functional adaptive CD4 Foxp3 T cells develop in MHC class II-deficient mice.
120 17142726 CD4 Foxp3 regulatory T (T(R)) cells are well-defined regulator T cells known to develop in the thymus through positive selection by medium-to-high affinity TCR-MHC interactions.
121 17142726 CD4 Foxp3 T(R) cells are found in secondary lymphoid tissues (spleen and lymph nodes) and peripheral tissues (liver) but not the thymus of severely MHC class II-deficient (Aalpha(-/-) B6) mice.
122 17142726 Furthermore, these T(R) cells suppress IL-2 release and proliferative responses in vitro of naive CD25(-) (CD4 or CD8) T cells from normal B6 mice primed by bead-coupled anti-CD3/anti-CD28 Ab as efficiently as CD4CD25(high) T(R) cells from congenic, normal B6 mice.
123 17142726 MHC class II-independent CD4 Foxp3(+) T(R) cells thus preferentially express the (TGF-beta-induced) integrin molecule alpha(E) (CD103), are generated mainly in the periphery and efficiently mediate immunosuppressive effects.
124 17204242 These regulatory T cells are phenotypically unique in their expression of Foxp3, IL-10, and IFN-gamma.
125 17237429 To ascertain T(reg) cell dependency, a kinetic analysis was performed showing increased levels of FoxP3(+)CD25(+)CD4(+) T cells.
126 17299718 Immunosuppression during active tuberculosis is characterized by decreased interferon- gamma production and CD25 expression with elevated forkhead box P3, transforming growth factor- beta , and interleukin-4 mRNA levels.
127 17299718 All 3 groups displayed BCG-induced increases in effector and regulatory T cell phenotypes as defined by CD4(+)CD25(lo) and CD4(+)CD25(hi) T cells, respectively.
128 17299718 In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4(+)CD25(hi), CTLA-4, and interferon- gamma .
129 17299718 However, these case patients expressed the highest mRNA levels of forkhead box P3, transforming growth factor (TGF)- beta , and interleukin (IL)-4 and a lower T-bet : GATA-3 ratio.
130 17299718 There were no significant differences in IL-4 delta 2, IL-10, or TGF- beta receptor-II mRNA expression between groups.
131 17299718 Immunosuppression during active tuberculosis is characterized by decreased interferon- gamma production and CD25 expression with elevated forkhead box P3, transforming growth factor- beta , and interleukin-4 mRNA levels.
132 17299718 All 3 groups displayed BCG-induced increases in effector and regulatory T cell phenotypes as defined by CD4(+)CD25(lo) and CD4(+)CD25(hi) T cells, respectively.
133 17299718 In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4(+)CD25(hi), CTLA-4, and interferon- gamma .
134 17299718 However, these case patients expressed the highest mRNA levels of forkhead box P3, transforming growth factor (TGF)- beta , and interleukin (IL)-4 and a lower T-bet : GATA-3 ratio.
135 17299718 There were no significant differences in IL-4 delta 2, IL-10, or TGF- beta receptor-II mRNA expression between groups.
136 17317581 Tumor protective immunity in the transplant recipients was dependent on CD4(+) and CD8(+) T cells, and tumor-reactive T cells in the spleens of vaccinated mice could be detected in IFN-gamma enzyme-linked immunosorbent spot (ELISPOT) assays.
137 17317581 Adoptive transfer of T cells accelerated T cell reconstitution, but it also resulted in increased percentages of CD4(+)CD25(+)Foxp3(+) cells soon after HSCT.
138 17317581 Treatment of HSC transplant recipients with an anti-CD25 mAb before tumor vaccination inhibited antitumor immunity and significantly decreased the number of IFN-gamma-secreting tumor-specific CD4 T cells.
139 17384578 The results indicated that CD8+ T cells were predominant and that T-regulatory cells (FoxP3+, CD4/CD25+, CD4/CD62L(high), CD4/CTLA-4e) were relatively deficient in the regressing tumors.
140 17440723 Furthermore, a significantly reduced proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells was detected by flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX.
141 17440723 Thus, a single administration of low dose CTX could augment antitumor immune responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ Treg cells in tumor-bearing mice.
142 17440723 Furthermore, a significantly reduced proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells was detected by flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX.
143 17440723 Thus, a single administration of low dose CTX could augment antitumor immune responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ Treg cells in tumor-bearing mice.
144 17473370 Vaccination efficacy can be amplified by depleting CD4;+CD25;+Foxp3;+ regulatory T cells (Treg), but the risk of inducing autoimmunity warrants new strategies to selectively amplify anti-tumor immunity when modulating Treg.
145 17473370 In the tumors, the major cyclooxygenase (COX)-2 product is prostaglandin E2(PGE2) which suppresses T and NK cells while amplifying Treg.
146 17475646 Functional Foxp3+ CD4+ CD25(Bright+) "natural" regulatory T cells are abundant in rabbit conjunctiva and suppress virus-specific CD4+ and CD8+ effector T cells during ocular herpes infection.
147 17475646 We studied the phenotype and distribution of "naturally" occurring CD4(+) CD25(+) T regulatory cells (CD4(+) CD25(+) nT(reg) cells) resident in rabbit conjunctiva, the main T-cell inductive site of the ocular mucosal immune system, and we investigated their suppressive capacities using herpes simplex virus type 1 (HSV-1)-specific effector T (T(eff)) cells induced during ocular infection.
148 17475646 The expression of CD4, CD25, CTLA4, GITR, and Foxp3 was examined by reverse transcription-PCR, Western blotting, and fluorescence-activated cell sorter analysis in CD45(+) pan-leukocytes isolated from conjunctiva, spleen, and peripheral blood monocyte cells (PBMC) of HSV-1-infected and uninfected rabbits.
149 17475646 Normal conjunctiva showed a higher frequency of CD4(+) CD25((Bright+)) T cells than did spleen and PBMC.
150 17475646 These cells expressed high levels of Foxp3, GITR, and CTLA4 molecules.
151 17475646 CD4(+) CD25((Bright+)) T cells were localized continuously along the upper and lower palpebral and bulbar conjunctiva, throughout the epithelium and substantia propria.
152 17475646 Conjunctiva-derived CD4(+) CD25((Bright+)) T cells, but not CD4(+) CD25((low)) T cells, efficiently suppressed HSV-specific CD4(+) and CD8(+) T(eff) cells.
153 17475646 The CD4(+) CD25((Bright+)) T-cell-mediated suppression was effective on both peripheral blood and conjunctiva infiltrating T(eff) cells and was cell-cell contact dependent but independent of interleukin-10 and transforming growth factor beta.
154 17475646 Interestingly, during an ocular herpes infection, there was a selective increase in the frequency and suppressive capacity of Foxp3(+) CD4(+) CD25((Bright+)) T cells in conjunctiva but not in the spleen or in peripheral blood.
155 17475646 Altogether, these results provide the first evidence that functional Foxp3(+) CD4(+) CD25((Bright+)) T(reg) cells accumulate in the conjunctiva.
156 17475646 It remains to be determined whether conjunctiva CD4(+) CD25(+) nT(reg) cells affect the topical/mucosal delivery of subunit vaccines that stimulate the ocular mucosal immune system.
157 17475646 Functional Foxp3+ CD4+ CD25(Bright+) "natural" regulatory T cells are abundant in rabbit conjunctiva and suppress virus-specific CD4+ and CD8+ effector T cells during ocular herpes infection.
158 17475646 We studied the phenotype and distribution of "naturally" occurring CD4(+) CD25(+) T regulatory cells (CD4(+) CD25(+) nT(reg) cells) resident in rabbit conjunctiva, the main T-cell inductive site of the ocular mucosal immune system, and we investigated their suppressive capacities using herpes simplex virus type 1 (HSV-1)-specific effector T (T(eff)) cells induced during ocular infection.
159 17475646 The expression of CD4, CD25, CTLA4, GITR, and Foxp3 was examined by reverse transcription-PCR, Western blotting, and fluorescence-activated cell sorter analysis in CD45(+) pan-leukocytes isolated from conjunctiva, spleen, and peripheral blood monocyte cells (PBMC) of HSV-1-infected and uninfected rabbits.
160 17475646 Normal conjunctiva showed a higher frequency of CD4(+) CD25((Bright+)) T cells than did spleen and PBMC.
161 17475646 These cells expressed high levels of Foxp3, GITR, and CTLA4 molecules.
162 17475646 CD4(+) CD25((Bright+)) T cells were localized continuously along the upper and lower palpebral and bulbar conjunctiva, throughout the epithelium and substantia propria.
163 17475646 Conjunctiva-derived CD4(+) CD25((Bright+)) T cells, but not CD4(+) CD25((low)) T cells, efficiently suppressed HSV-specific CD4(+) and CD8(+) T(eff) cells.
164 17475646 The CD4(+) CD25((Bright+)) T-cell-mediated suppression was effective on both peripheral blood and conjunctiva infiltrating T(eff) cells and was cell-cell contact dependent but independent of interleukin-10 and transforming growth factor beta.
165 17475646 Interestingly, during an ocular herpes infection, there was a selective increase in the frequency and suppressive capacity of Foxp3(+) CD4(+) CD25((Bright+)) T cells in conjunctiva but not in the spleen or in peripheral blood.
166 17475646 Altogether, these results provide the first evidence that functional Foxp3(+) CD4(+) CD25((Bright+)) T(reg) cells accumulate in the conjunctiva.
167 17475646 It remains to be determined whether conjunctiva CD4(+) CD25(+) nT(reg) cells affect the topical/mucosal delivery of subunit vaccines that stimulate the ocular mucosal immune system.
168 17475646 Functional Foxp3+ CD4+ CD25(Bright+) "natural" regulatory T cells are abundant in rabbit conjunctiva and suppress virus-specific CD4+ and CD8+ effector T cells during ocular herpes infection.
169 17475646 We studied the phenotype and distribution of "naturally" occurring CD4(+) CD25(+) T regulatory cells (CD4(+) CD25(+) nT(reg) cells) resident in rabbit conjunctiva, the main T-cell inductive site of the ocular mucosal immune system, and we investigated their suppressive capacities using herpes simplex virus type 1 (HSV-1)-specific effector T (T(eff)) cells induced during ocular infection.
170 17475646 The expression of CD4, CD25, CTLA4, GITR, and Foxp3 was examined by reverse transcription-PCR, Western blotting, and fluorescence-activated cell sorter analysis in CD45(+) pan-leukocytes isolated from conjunctiva, spleen, and peripheral blood monocyte cells (PBMC) of HSV-1-infected and uninfected rabbits.
171 17475646 Normal conjunctiva showed a higher frequency of CD4(+) CD25((Bright+)) T cells than did spleen and PBMC.
172 17475646 These cells expressed high levels of Foxp3, GITR, and CTLA4 molecules.
173 17475646 CD4(+) CD25((Bright+)) T cells were localized continuously along the upper and lower palpebral and bulbar conjunctiva, throughout the epithelium and substantia propria.
174 17475646 Conjunctiva-derived CD4(+) CD25((Bright+)) T cells, but not CD4(+) CD25((low)) T cells, efficiently suppressed HSV-specific CD4(+) and CD8(+) T(eff) cells.
175 17475646 The CD4(+) CD25((Bright+)) T-cell-mediated suppression was effective on both peripheral blood and conjunctiva infiltrating T(eff) cells and was cell-cell contact dependent but independent of interleukin-10 and transforming growth factor beta.
176 17475646 Interestingly, during an ocular herpes infection, there was a selective increase in the frequency and suppressive capacity of Foxp3(+) CD4(+) CD25((Bright+)) T cells in conjunctiva but not in the spleen or in peripheral blood.
177 17475646 Altogether, these results provide the first evidence that functional Foxp3(+) CD4(+) CD25((Bright+)) T(reg) cells accumulate in the conjunctiva.
178 17475646 It remains to be determined whether conjunctiva CD4(+) CD25(+) nT(reg) cells affect the topical/mucosal delivery of subunit vaccines that stimulate the ocular mucosal immune system.
179 17475646 Functional Foxp3+ CD4+ CD25(Bright+) "natural" regulatory T cells are abundant in rabbit conjunctiva and suppress virus-specific CD4+ and CD8+ effector T cells during ocular herpes infection.
180 17475646 We studied the phenotype and distribution of "naturally" occurring CD4(+) CD25(+) T regulatory cells (CD4(+) CD25(+) nT(reg) cells) resident in rabbit conjunctiva, the main T-cell inductive site of the ocular mucosal immune system, and we investigated their suppressive capacities using herpes simplex virus type 1 (HSV-1)-specific effector T (T(eff)) cells induced during ocular infection.
181 17475646 The expression of CD4, CD25, CTLA4, GITR, and Foxp3 was examined by reverse transcription-PCR, Western blotting, and fluorescence-activated cell sorter analysis in CD45(+) pan-leukocytes isolated from conjunctiva, spleen, and peripheral blood monocyte cells (PBMC) of HSV-1-infected and uninfected rabbits.
182 17475646 Normal conjunctiva showed a higher frequency of CD4(+) CD25((Bright+)) T cells than did spleen and PBMC.
183 17475646 These cells expressed high levels of Foxp3, GITR, and CTLA4 molecules.
184 17475646 CD4(+) CD25((Bright+)) T cells were localized continuously along the upper and lower palpebral and bulbar conjunctiva, throughout the epithelium and substantia propria.
185 17475646 Conjunctiva-derived CD4(+) CD25((Bright+)) T cells, but not CD4(+) CD25((low)) T cells, efficiently suppressed HSV-specific CD4(+) and CD8(+) T(eff) cells.
186 17475646 The CD4(+) CD25((Bright+)) T-cell-mediated suppression was effective on both peripheral blood and conjunctiva infiltrating T(eff) cells and was cell-cell contact dependent but independent of interleukin-10 and transforming growth factor beta.
187 17475646 Interestingly, during an ocular herpes infection, there was a selective increase in the frequency and suppressive capacity of Foxp3(+) CD4(+) CD25((Bright+)) T cells in conjunctiva but not in the spleen or in peripheral blood.
188 17475646 Altogether, these results provide the first evidence that functional Foxp3(+) CD4(+) CD25((Bright+)) T(reg) cells accumulate in the conjunctiva.
189 17475646 It remains to be determined whether conjunctiva CD4(+) CD25(+) nT(reg) cells affect the topical/mucosal delivery of subunit vaccines that stimulate the ocular mucosal immune system.
190 17475646 Functional Foxp3+ CD4+ CD25(Bright+) "natural" regulatory T cells are abundant in rabbit conjunctiva and suppress virus-specific CD4+ and CD8+ effector T cells during ocular herpes infection.
191 17475646 We studied the phenotype and distribution of "naturally" occurring CD4(+) CD25(+) T regulatory cells (CD4(+) CD25(+) nT(reg) cells) resident in rabbit conjunctiva, the main T-cell inductive site of the ocular mucosal immune system, and we investigated their suppressive capacities using herpes simplex virus type 1 (HSV-1)-specific effector T (T(eff)) cells induced during ocular infection.
192 17475646 The expression of CD4, CD25, CTLA4, GITR, and Foxp3 was examined by reverse transcription-PCR, Western blotting, and fluorescence-activated cell sorter analysis in CD45(+) pan-leukocytes isolated from conjunctiva, spleen, and peripheral blood monocyte cells (PBMC) of HSV-1-infected and uninfected rabbits.
193 17475646 Normal conjunctiva showed a higher frequency of CD4(+) CD25((Bright+)) T cells than did spleen and PBMC.
194 17475646 These cells expressed high levels of Foxp3, GITR, and CTLA4 molecules.
195 17475646 CD4(+) CD25((Bright+)) T cells were localized continuously along the upper and lower palpebral and bulbar conjunctiva, throughout the epithelium and substantia propria.
196 17475646 Conjunctiva-derived CD4(+) CD25((Bright+)) T cells, but not CD4(+) CD25((low)) T cells, efficiently suppressed HSV-specific CD4(+) and CD8(+) T(eff) cells.
197 17475646 The CD4(+) CD25((Bright+)) T-cell-mediated suppression was effective on both peripheral blood and conjunctiva infiltrating T(eff) cells and was cell-cell contact dependent but independent of interleukin-10 and transforming growth factor beta.
198 17475646 Interestingly, during an ocular herpes infection, there was a selective increase in the frequency and suppressive capacity of Foxp3(+) CD4(+) CD25((Bright+)) T cells in conjunctiva but not in the spleen or in peripheral blood.
199 17475646 Altogether, these results provide the first evidence that functional Foxp3(+) CD4(+) CD25((Bright+)) T(reg) cells accumulate in the conjunctiva.
200 17475646 It remains to be determined whether conjunctiva CD4(+) CD25(+) nT(reg) cells affect the topical/mucosal delivery of subunit vaccines that stimulate the ocular mucosal immune system.
201 17513751 In this report, we describe the ability of maturation-resistant, rapamycin (RAPA)-conditioned DC, which are markedly impaired in Foxp3(-) T cell allostimulatory capacity, to favor the stimulation of murine alloantigen-specific CD4(+)CD25(+)Foxp3(+) Treg.
202 17513751 This was associated with graft infiltration by CD4(+)Foxp3(+) Treg and the absence of transplant vasculopathy.
203 17513751 In this report, we describe the ability of maturation-resistant, rapamycin (RAPA)-conditioned DC, which are markedly impaired in Foxp3(-) T cell allostimulatory capacity, to favor the stimulation of murine alloantigen-specific CD4(+)CD25(+)Foxp3(+) Treg.
204 17513751 This was associated with graft infiltration by CD4(+)Foxp3(+) Treg and the absence of transplant vasculopathy.
205 17616639 CD4+CD25+Foxp3+ regulatory T (Treg) cells have been implicated in the lack of effective antitumor immunity.
206 17851131 Increased frequency of CD4(+)CD25(high) Treg cells inhibit BCG-specific induction of IFN-gamma by CD4(+) T cells from TB patients.
207 17851131 The immune response to tuberculosis (TB) was dominated by both CD4(+) T cells with the T helper 1 type cytokines and CD8(+) T cells.
208 17851131 Recent studies have suggested that the circumstances in which protective or tissue-damaging T cell responses to microbes are affected by the activity of Treg (CD4(+)CD25(high)) cells.
209 17851131 In the present study, we demonstrated that the frequencies of CD4(+)CD25(+) and CD4(+)CD25(high) T cells in TB patients were significantly higher compared to normal individuals.
210 17851131 These Treg cells expressed CTLA-4 and Foxp3 at protein level and displayed activation and memory phenotypes as assessed by flow cytometric analysis.
211 17851131 The frequencies of CD4(+)CD25(high)CTLA-4(+) and CD4(+)CD25(high)Foxp3(+) T cells within the total CD4(+) T cell population were significantly increased in the blood of TB patients compared to healthy donors.
212 17851131 The phenotypic analysis demonstrated that CD4(+)CD25(high) Treg expressed higher levels of CD45RO and HLA-DR, and lower levels of CD45RA compared to CD4(+)CD25(low) and CD4(+)CD25(-) T cells.
213 17851131 The addition of CD4(+)CD25(high) T cells back to cultures could significantly suppress the antigen-specific production of IFN-gamma induced by BCG-stimulated CD4(+)CD25(-) T cells, suggesting that Treg might play a key role in the control of cellular immune responses in TB infection.
214 17851131 Increased frequency of CD4(+)CD25(high) Treg cells inhibit BCG-specific induction of IFN-gamma by CD4(+) T cells from TB patients.
215 17851131 The immune response to tuberculosis (TB) was dominated by both CD4(+) T cells with the T helper 1 type cytokines and CD8(+) T cells.
216 17851131 Recent studies have suggested that the circumstances in which protective or tissue-damaging T cell responses to microbes are affected by the activity of Treg (CD4(+)CD25(high)) cells.
217 17851131 In the present study, we demonstrated that the frequencies of CD4(+)CD25(+) and CD4(+)CD25(high) T cells in TB patients were significantly higher compared to normal individuals.
218 17851131 These Treg cells expressed CTLA-4 and Foxp3 at protein level and displayed activation and memory phenotypes as assessed by flow cytometric analysis.
219 17851131 The frequencies of CD4(+)CD25(high)CTLA-4(+) and CD4(+)CD25(high)Foxp3(+) T cells within the total CD4(+) T cell population were significantly increased in the blood of TB patients compared to healthy donors.
220 17851131 The phenotypic analysis demonstrated that CD4(+)CD25(high) Treg expressed higher levels of CD45RO and HLA-DR, and lower levels of CD45RA compared to CD4(+)CD25(low) and CD4(+)CD25(-) T cells.
221 17851131 The addition of CD4(+)CD25(high) T cells back to cultures could significantly suppress the antigen-specific production of IFN-gamma induced by BCG-stimulated CD4(+)CD25(-) T cells, suggesting that Treg might play a key role in the control of cellular immune responses in TB infection.
222 17897047 To ascertain whether the observed immune deviation was in part supported by T(reg) cells, analysis revealed involvement of FoxP3(+) CD25(+) CD4(+) T cells.
223 17897047 Partial protection to EAE was also achieved by the adoptive transfer of CD25(-) CD4(+) T cells, suggesting that Th2 cells also contributed.
224 17944900 After three or four injections, most vaccinated MS subjects developed high frequencies of circulating interleukin (IL)-10-secreting T cells specific for the injected TCR peptides and significantly enhanced expression of FoxP3 by regulatory T cells present in both 'native' CD4+ CD25+ and 'inducible' CD4+ CD25- peripheral blood mononuclear cells (PBMC).
225 17957814 At the same time, co-immunization reduced the production of inflammatory cytokine, IFN-gamma, and increased the productions of IL-10 and FoxP3 in CD4 T cells, suggesting the anti-inflammation may be via a T regulatory function.
226 17982065 NIMA(d)-exposed splenocytes exhibited bystander suppression of tetanus-specific delayed-type hypersensitivity responses, which was reversed with Abs to TGF-beta and IL-10.
227 17982065 Rejector and acceptor NIMA(d)-exposed mice had reduced T effector responses and increased Foxp3(+) T(R) cells (CD4(+)CD25(+)Foxp3(+) T(R)) in spleen and lymph nodes compared with controls.
228 17982065 The key features distinguishing NIMA(d)-exposed acceptors from all other mice were: 1) higher frequency of IL-10- and TGF-beta-producing cells primarily in the CD4(+)CD25(+) T cell subset within lymph nodes and allografts, 2) a suppressed delayed-type hypersensitivity response to B6D2F1 Ags, and 3) allografts enriched in LAP(+), Foxp3(+), and CD4(+) T cells, with few CD8(+) T cells.
229 17982065 NIMA(d)-exposed splenocytes exhibited bystander suppression of tetanus-specific delayed-type hypersensitivity responses, which was reversed with Abs to TGF-beta and IL-10.
230 17982065 Rejector and acceptor NIMA(d)-exposed mice had reduced T effector responses and increased Foxp3(+) T(R) cells (CD4(+)CD25(+)Foxp3(+) T(R)) in spleen and lymph nodes compared with controls.
231 17982065 The key features distinguishing NIMA(d)-exposed acceptors from all other mice were: 1) higher frequency of IL-10- and TGF-beta-producing cells primarily in the CD4(+)CD25(+) T cell subset within lymph nodes and allografts, 2) a suppressed delayed-type hypersensitivity response to B6D2F1 Ags, and 3) allografts enriched in LAP(+), Foxp3(+), and CD4(+) T cells, with few CD8(+) T cells.
232 17997199 This Th1 shift was supported by an increased T-bet/GATA3 mRNA ratio.
233 17997199 IL-5 production within the airways was suppressed after the pretreatment with rCTB-Bet v 1, while local allergen-specific IgA antibodies were markedly enhanced by pretreatment with the construct.
234 17997199 Upregulation of Foxp3, IL-10 and TGF-beta mRNA expression was detected in splenocytes after pretreatment with unconjugated allergen but not with the fusion molecule, indicating that antigen conjugation to a mucosal carrier modifies the immunomodulating properties of an antigen/allergen.
235 18025169 We have previously shown that rSbsC-Bet v 1, the recombinant fusion protein of a bacterial surface (S-layer) protein of Geobacillus stearothermophilus ATCC 12980 and the major birch pollen allergen Bet v 1, exhibited reduced allergenicity and induced IFN-gamma and IL-10 synthesis in Bet v 1-specific Th2 clones.
236 18025169 In this study, we characterized the effects of rSbsC-Bet v 1 on immature monocyte-derived dendritic cells (mdDC) and the consequences for the polarization of naive CD4(+) T lymphocytes isolated from the blood of birch pollen-allergic patients. mdDC responded to rSbsC-Bet v 1 with a significant up-regulation of costimulatory molecules, functional maturation, and the synthesis of IL-10 and IL-12. mdDC matured with rSbsC-Bet v 1 induced the differentiation of naive T cells into IFN-gamma-producing cells.
237 18025169 In parallel, a substantial number of naive T cells developed into IL-10-producing CD25(+)Foxp3(+)CLTA-4(+) cells capable of active suppression.
238 18033300 Here we demonstrate that Epstein-Barr-virus-induced gene 3 (Ebi3, which encodes IL-27beta) and interleukin-12 alpha (Il12a, which encodes IL-12alpha/p35) are highly expressed by mouse Foxp3+ (forkhead box P3) T(reg) cells but not by resting or activated effector CD4+ T (T(eff)) cells, and that an Ebi3-IL-12alpha heterodimer is constitutively secreted by T(reg) but not T(eff) cells.
239 18033300 Both Ebi3 and Il12a messenger RNA are markedly upregulated in T(reg) cells co-cultured with T(eff) cells, thereby boosting Ebi3 and IL-12alpha production in trans.
240 18033300 T(reg)-cell restriction of this cytokine occurs because Ebi3 is a downstream target of Foxp3, a transcription factor that is required for T(reg)-cell development and function.
241 18033300 Here we demonstrate that Epstein-Barr-virus-induced gene 3 (Ebi3, which encodes IL-27beta) and interleukin-12 alpha (Il12a, which encodes IL-12alpha/p35) are highly expressed by mouse Foxp3+ (forkhead box P3) T(reg) cells but not by resting or activated effector CD4+ T (T(eff)) cells, and that an Ebi3-IL-12alpha heterodimer is constitutively secreted by T(reg) but not T(eff) cells.
242 18033300 Both Ebi3 and Il12a messenger RNA are markedly upregulated in T(reg) cells co-cultured with T(eff) cells, thereby boosting Ebi3 and IL-12alpha production in trans.
243 18033300 T(reg)-cell restriction of this cytokine occurs because Ebi3 is a downstream target of Foxp3, a transcription factor that is required for T(reg)-cell development and function.
244 18058571 Targeting CD4+CD25+FoxP3+ regulatory T-cells for the augmentation of cancer immunotherapy.
245 18058571 CD4+CD25+FoxP3+ T-regulatory (Treg) cells are vital to the maintenance of peripheral self tolerance and are implicated in tolerance to foreign antigens.
246 18058571 Targeting CD4+CD25+FoxP3+ regulatory T-cells for the augmentation of cancer immunotherapy.
247 18058571 CD4+CD25+FoxP3+ T-regulatory (Treg) cells are vital to the maintenance of peripheral self tolerance and are implicated in tolerance to foreign antigens.
248 18157008 Enhanced immunity to the neoplasm mediated predominantly by CD4+, CD8+, and NK/LAK cells was generated in the spleens of mice injected intracerebrally into the tumor bed with cells from the enriched vaccine, which translated into prolonged survival.
249 18157008 Regulatory T cells (CD4+CD25+Foxp3+-positive) were relatively deficient in the spleen cells from tumor-bearing mice injected intracerebrally with the enriched vaccine.
250 18172322 Peripheral T-cell tolerance associated with prostate cancer is independent from CD4+CD25+ regulatory T cells.
251 18172322 CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) are thought to suppress the natural and vaccine-induced immune response against tumor-associated antigens (TAA).
252 18283628 Here we report on the IN VITRO findings of a vaccination trial in five MTC patients, who were treated with a new DC generation protocol consisting of granulocyte-macrophage colony-stimulating factor and interferon-alpha (IFN-DCs).
253 18283628 In two patients who responded to therapy we found a large increase (in mean 2.9+/-1.9%) of antigen-specific IFN-gamma-secreting CD4+ cells as well as an increase of granzyme B positive CD8+ cells (mean 2.2+/-0.2%) in the peripheral blood.
254 18283628 In parallel, a decrease of CD4+/CD25+/FoxP3+ regulatory T cells was seen.
255 18286284 Also, chemotherapy represents one of several options available for clearance of CD4+ Foxp3+ regulatory T cells.
256 18323802 Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response.
257 18323802 We observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic cells in five patients, three patients showed a stable disease and four patients progressed despite DC vaccination.
258 18323802 A significant increase of specific cytotoxic CD8+ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin was detected in four patients after DC vaccination.
259 18323802 In patients with a clinical response, an increase of interleukin 12 (IL-12) serum levels and a decrease of the frequency of CD4+CD25(+)FOXP3+ T regulatory cells were observed.
260 18323802 Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response.
261 18323802 We observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic cells in five patients, three patients showed a stable disease and four patients progressed despite DC vaccination.
262 18323802 A significant increase of specific cytotoxic CD8+ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin was detected in four patients after DC vaccination.
263 18323802 In patients with a clinical response, an increase of interleukin 12 (IL-12) serum levels and a decrease of the frequency of CD4+CD25(+)FOXP3+ T regulatory cells were observed.
264 18354238 IL-2/anti-IL-2 antibody complex enhances vaccine-mediated antigen-specific CD8+ T cell responses and increases the ratio of effector/memory CD8+ T cells to regulatory T cells.
265 18354238 IL-2 is well described as a cytokine with two markedly distinct functionalities: as a necessary signal during CD4(+) and CD8(+) T cell activation/expansion and as an essential cytokine for the maintenance of CD4(+)CD25(+)FoxP3(+) T cells (regulatory T (T(REG)) cells) during homeostasis.
266 18354238 IL-2 complex led to an increase in the number of Ag-specific effector/memory CD8(+) T cells, cytokine production, and CTL lysis following Ag-specific restimulation in a vaccination setting.
267 18354238 Moreover, in contrast to the use of IL-2 alone, IL-2 complex greatly increased the ratio of effector/memory CD8(+) T cells to T(REG) cells.
268 18390718 The amelioration of AIH was directly related to the induction of a specific population of flea antigenic specific T cells exhibiting a CD4(+)CD25(-)FoxP3(+) phenotype, a characteristic of regulatory T (T(REG)) cells.
269 18390718 These T(REG) cells expressing IL-10, IFN-gamma, and the transcriptional factor T-bet after Ag stimulation were driven by a tolerogenic MHC class II(+)/CD40(low) dendritic cell population that was induced by the coimmunization of DNA and protein vaccines.
270 18390718 The tolerogenic dendritic cell could educate the naive T cells into CD4(+)CD25(-)FoxP3(+) T(REG) cells both in vitro and in vivo.
271 18390718 The amelioration of AIH was directly related to the induction of a specific population of flea antigenic specific T cells exhibiting a CD4(+)CD25(-)FoxP3(+) phenotype, a characteristic of regulatory T (T(REG)) cells.
272 18390718 These T(REG) cells expressing IL-10, IFN-gamma, and the transcriptional factor T-bet after Ag stimulation were driven by a tolerogenic MHC class II(+)/CD40(low) dendritic cell population that was induced by the coimmunization of DNA and protein vaccines.
273 18390718 The tolerogenic dendritic cell could educate the naive T cells into CD4(+)CD25(-)FoxP3(+) T(REG) cells both in vitro and in vivo.
274 18390744 We previously demonstrated that HIV envelope glycoprotein (Env), delivered in the form of a vaccine and expressed by dendritic cells or 293T cells, could suppress Ag-stimulated CD4(+) T cell proliferation.
275 18390744 Recently, CD4(+) regulatory T (Treg) cells were found to inhibit protective anti-HIV CD4(+) and CD8(+) T cell responses.
276 18390744 Depletion of CD25(+) Treg cells from PBMC did not overcome the Env-induced suppression of CD4(+) T cell proliferation, demonstrating that CD25(+)FoxP3(+) Treg cells are not involved in Env-induced suppression of CD4(+) T cell proliferation.
277 18401437 Thus, in the current study we hypothesize that the cluster intradermal CRT/E7 DNA vaccination will generate significant antigen-specific CD8+ T-cell infiltrates in E7-expressing tumors in tumor-bearing mice, leading to an increase in apoptotic tumor cell death.
278 18401437 We found that cluster intradermal CRT/E7 DNA vaccination is capable of rapidly generating a significant number of E7-specific CD8+ T cells, resulting in significant therapeutic antitumor effects in vaccinated mice.
279 18401437 We also observed that cluster intradermal CRT/E7 DNA vaccination in the presence of tumor generates significantly higher E7-specific CD8+ T-cell immune responses in the systemic circulation as well as in the tumors.
280 18401437 In addition, this vaccination regimen also led to significantly lower levels of CD4+Foxp3+ T-regulatory cells and myeloid suppressor cells compared to vaccination with CRT DNA in peripheral blood and in tumor-infiltrating lymphocytes, resulting in an increase in apoptotic tumor cell death.
281 18419605 Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells.
282 18419605 In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)-beta and interleukin (IL)-10 double-positive CD4(+) T cells within 1 week of autologous DC/T cell co-cultures.
283 18419605 In iDC/T cell cultures, where antigen-specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF-beta and IL-10 secreted by CD4(+)CD25(-)FOXP3(-) T cells.
284 18419605 In addition, the suppressive capacity of CD4(+) T cells conditioned by iDC was transferable to already primed antigen-specific CD8(+) T cell cultures.
285 18419605 In contrast, addition of CD4(+) T cells conditioned by mDC to primed antigen-specific CD8(+) T cells resulted in enhanced CD8(+) T cell responses, notwithstanding the presence of TGF-beta(+)/IL-10(+) T cells in the transferred fraction.
286 18419605 We show that iDC-conditioned CD4(+) T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4(+) T cells.
287 18419605 Furthermore, TGF-beta(+)/IL-10(+) T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.
288 18468739 In vitro restimulation with antigen-pulsed bone marrow-derived dendritic cells (BMDCs) induced remarkable T-cell proliferative response specific for both VP1 and EGFP antigen and IL-2 and IFN-gamma production.
289 18468739 After intranasal administration of EGFP-VLPs, as well as after polyomavirus infection, a moderate reduction of CD4(+)CD25(+)Foxp3(+) T cells was observed in spleens but not in lymph nodes and peripheral blood, suggesting that both MPyV virions and pseudocapsids are able to induce changes in distribution of regulatory T cells.
290 18493984 IL-2 induces in vivo suppression by CD4(+)CD25(+)Foxp3(+) regulatory T cells.
291 18493984 At the same time, IL-2 is essential for the peripheral homeostasis of CD4(+)CD25(+)Foxp3(+ )regulatory T cells (Treg).
292 18493984 IL-2 treatment induces Treg expansion as well as IL-10 production and increases their suppressive potential in vitro.
293 18493984 The suppressive effect can be transferred onto naive animals by Treg from IL-2-treated mice and the suppression depends on the synergistic action of IL-10 and TGF-beta.
294 18493984 IL-2 induces in vivo suppression by CD4(+)CD25(+)Foxp3(+) regulatory T cells.
295 18493984 At the same time, IL-2 is essential for the peripheral homeostasis of CD4(+)CD25(+)Foxp3(+ )regulatory T cells (Treg).
296 18493984 IL-2 treatment induces Treg expansion as well as IL-10 production and increases their suppressive potential in vitro.
297 18493984 The suppressive effect can be transferred onto naive animals by Treg from IL-2-treated mice and the suppression depends on the synergistic action of IL-10 and TGF-beta.
298 18519811 CD4(+)CD25(high)FoxP3(+) regulatory T (Treg) cells limit antigen-specific immune responses and are a cause of suppressed anticancer immunity.
299 18519811 By flow cytometric analysis, we report the first direct evidence that circulating CD4(+)CD25(high)FoxP3(+) Treg cells are depleted after multiple doses of denileukin diftitox.
300 18519811 CD4(+)CD25(high)FoxP3(+) regulatory T (Treg) cells limit antigen-specific immune responses and are a cause of suppressed anticancer immunity.
301 18519811 By flow cytometric analysis, we report the first direct evidence that circulating CD4(+)CD25(high)FoxP3(+) Treg cells are depleted after multiple doses of denileukin diftitox.
302 18566377 Down-regulation of CD4+CD25+ regulatory T (Treg) cell function might be beneficial to enhance the immunogenicity of viral and tumor vaccines or to induce breakdown of immunotolerance.
303 18566377 In this study, we show that P17, a short synthetic peptide that inhibits TGF-beta1 and TGF-beta2 developed in our laboratory, is able to inhibit Treg activity in vitro and in vivo.
304 18566377 EG.7-OVA tumors, administration of P17 improved their proliferation, reduced the number of CD4+Foxp3+ T cells, and inhibited tumor growth.
305 18566447 However, DC/breast cancer fusions stimulate a mixed T cell response characterized by the expansion of both activated and regulatory T cell populations, the latter of which is characterized by expression of CTLA-4, FOXP3, IL-10, and the suppression of T cell responses.
306 18566447 Our results demonstrate that IL-12, IL-18, and TLR 9 agonist CpG oligodeoxynucleotides reduce the level of fusion-mediated regulatory T cell expansion.
307 18579694 Differential expression of interleukin-4 (IL-4) and IL-4 delta 2 mRNA, but not transforming growth factor beta (TGF-beta), TGF-beta RII, Foxp3, gamma interferon, T-bet, or GATA-3 mRNA, in patients with fast and slow responses to antituberculosis treatment.
308 18579694 This study investigated interleukin-4 (IL-4), IL-4 delta 2, transforming growth factor beta (TGF-beta), TGF-beta RII, Foxp3, GATA-3, T-bet, and gamma interferon (IFN-gamma) transcription in peripheral blood samples of adult pulmonary tuberculosis patients prior to and after 1 week of therapy.
309 18579694 There were no significant differences in expression of TGF-beta, TGF-beta RII, Foxp3, IFN-gamma, and GATA-3 between the groups.
310 18579694 Differential expression of interleukin-4 (IL-4) and IL-4 delta 2 mRNA, but not transforming growth factor beta (TGF-beta), TGF-beta RII, Foxp3, gamma interferon, T-bet, or GATA-3 mRNA, in patients with fast and slow responses to antituberculosis treatment.
311 18579694 This study investigated interleukin-4 (IL-4), IL-4 delta 2, transforming growth factor beta (TGF-beta), TGF-beta RII, Foxp3, GATA-3, T-bet, and gamma interferon (IFN-gamma) transcription in peripheral blood samples of adult pulmonary tuberculosis patients prior to and after 1 week of therapy.
312 18579694 There were no significant differences in expression of TGF-beta, TGF-beta RII, Foxp3, IFN-gamma, and GATA-3 between the groups.
313 18579694 Differential expression of interleukin-4 (IL-4) and IL-4 delta 2 mRNA, but not transforming growth factor beta (TGF-beta), TGF-beta RII, Foxp3, gamma interferon, T-bet, or GATA-3 mRNA, in patients with fast and slow responses to antituberculosis treatment.
314 18579694 This study investigated interleukin-4 (IL-4), IL-4 delta 2, transforming growth factor beta (TGF-beta), TGF-beta RII, Foxp3, GATA-3, T-bet, and gamma interferon (IFN-gamma) transcription in peripheral blood samples of adult pulmonary tuberculosis patients prior to and after 1 week of therapy.
315 18579694 There were no significant differences in expression of TGF-beta, TGF-beta RII, Foxp3, IFN-gamma, and GATA-3 between the groups.
316 18641317 CD4 cells induced to express FoxP3, IL-10, and TGF-beta1 in response to TCR signaling and TGF-beta1 can reverse diabetes with clinical restoration of prediabetic serum levels of IL-10.
317 18676860 Importantly, they recognized HLA-DRB1*04-matched fresh leukemic cells expressing the WT1 antigen.
318 18676860 These clones exerted a T helper 2 cytokine profile, had a CD4(+)CD25(+)Foxp3(+)GITR(+)CD127(-) T(reg) phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact.
319 18676860 Furthermore, priming of T cells with the WT1-126 HLA-A0201-restricted peptide in the presence of T(regs) strongly inhibited the induction of anti-WT1-126 CD8(+) CTL responses as evidenced by both very low cytotoxic activity and IFN-gamma production.
320 18676860 Moreover, these T(reg) clones specifically produced granzyme B and selectively induced apoptosis in WT1-84-pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells.
321 18676860 Importantly, we have also detected anti-WT1-84 interleukin-5(+)/granzyme B(+)/Foxp3(+) CD4(+) T(regs) in five of eight HLA-DR4(+) acute myeloid leukemia patients.
322 18676860 Importantly, they recognized HLA-DRB1*04-matched fresh leukemic cells expressing the WT1 antigen.
323 18676860 These clones exerted a T helper 2 cytokine profile, had a CD4(+)CD25(+)Foxp3(+)GITR(+)CD127(-) T(reg) phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact.
324 18676860 Furthermore, priming of T cells with the WT1-126 HLA-A0201-restricted peptide in the presence of T(regs) strongly inhibited the induction of anti-WT1-126 CD8(+) CTL responses as evidenced by both very low cytotoxic activity and IFN-gamma production.
325 18676860 Moreover, these T(reg) clones specifically produced granzyme B and selectively induced apoptosis in WT1-84-pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells.
326 18676860 Importantly, we have also detected anti-WT1-84 interleukin-5(+)/granzyme B(+)/Foxp3(+) CD4(+) T(regs) in five of eight HLA-DR4(+) acute myeloid leukemia patients.
327 18707923 Expression of PD-1 is up-regulated in CD4+CD25+ FoxP3+ regulatory T cell of non-responders after hepatitis B surface antigen vaccine immunization.
328 18714045 Because TGF-beta is known to induce regulatory T cells (Tregs), we further showed that the DC/4T1+Adv-TGF-beta-R fusion vaccine induced fewer CD4(+)CD25(+)Foxp3(+) Tregs than the DC/4T1+Adv-LacZ fusion vaccine in vitro and in vivo.
329 18714045 The suppressive role of splenic CD4(+)CD25(+) Tregs isolated from mice immunized with DC/4T1+Adv-LacZ was demonstrated using a CTL killing assay.
330 18751426 The Tregs were defined based on their expression of CD4, CD25 and FOXP3, a transcription factor.
331 18809757 Clinical responses were significantly associated with a reduction in CD4(+)CD25(+)FOXP3(+) regulatory T cells, an increase in CD3(-)CD56(dim)CD16(+) natural killer (NK) cells, and maturation of lymphocytes to the effector memory stage in either postvaccination peripheral blood or tumor specimen samples.
332 18809757 In one HLA-A*0201(+) patient who achieved CR, IL-4 release by circulating T cells in response to tumor-specific IgH-encoded peptides was also documented.
333 18818761 Distinct effects of IL-18 on the engraftment and function of human effector CD8 T cells and regulatory T cells.
334 18818761 IL-18 enhanced the engraftment of human CD8(+) effector T cells and promoted the development of xenogeneic graft versus host disease (GVHD).
335 18818761 In marked contrast, IL-18 had reciprocal effects on the engraftment of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in the xenografted mice.
336 18818761 In vitro experiments indicated that the expression of the IL-18Ralpha was induced on both CD4 and CD8 effector T cells and Tregs, and that the duration of expression was less sustained on Tregs.
337 18827195 Throughout the infection (until 120 days), we monitored outcome (CFU), molecules involved in the development of immunoregulation (Foxp3, hemoxygenase 1, idoleamine 2,3-dioxygenase, and transforming growth factor beta [TGF-beta]), and indicators of cytokine balance (tumor necrosis factor, inducible nitric oxide synthase, interleukin-4 [IL-4], and IL-4delta2; an inhibitory splice variant of IL-4 associated with improved outcome in human TB).
338 18827195 Oral M. vaccae had a significant effect on CFU and led to increased expression of Th1 markers and of IL-4delta2, while suppressing IL-4, Foxp3, and TGF-beta.
339 18832651 Host CD4+CD25+ T cells can expand and comprise a major component of the Treg compartment after experimental HCT.
340 18832651 The present studies investigated the residual host CD4(+)CD25(+)Foxp3(+) (Treg) compartment after several conditioning regimens, including T cell-depleted and T cell-replete HCT and observed (1) a small number of recipient Treg cells survived aggressive conditioning; (2) the surviving, that is, residual Tregs underwent marked expansion; and (3) recipient CD4(+)FoxP3(+) cells composed the majority of the Treg compartment for several months post-syngeneic HCT.
341 18832651 These observations support the notion that functional host Tregs initially occupy a niche in lymphopenic transplantation recipients, undergo significant expansion, and contribute to the compartment for an extended period before donor-derived CD4(+)FoxP3(+) T cells eventually compose the majority of the compartment.
342 18832651 Host CD4+CD25+ T cells can expand and comprise a major component of the Treg compartment after experimental HCT.
343 18832651 The present studies investigated the residual host CD4(+)CD25(+)Foxp3(+) (Treg) compartment after several conditioning regimens, including T cell-depleted and T cell-replete HCT and observed (1) a small number of recipient Treg cells survived aggressive conditioning; (2) the surviving, that is, residual Tregs underwent marked expansion; and (3) recipient CD4(+)FoxP3(+) cells composed the majority of the Treg compartment for several months post-syngeneic HCT.
344 18832651 These observations support the notion that functional host Tregs initially occupy a niche in lymphopenic transplantation recipients, undergo significant expansion, and contribute to the compartment for an extended period before donor-derived CD4(+)FoxP3(+) T cells eventually compose the majority of the compartment.
345 18981115 Imatinib mesylate inhibits CD4+ CD25+ regulatory T cell activity and enhances active immunotherapy against BCR-ABL- tumors.
346 18981115 Suppressive as well as stimulating effects of this drug on CD4(+) and CD8(+) T lymphocytes or dendritic cells have been reported.
347 18981115 In the current study, we have investigated the influence of imatinib mesylate on CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg), a critical population of lymphocytes that contributes to peripheral tolerance.
348 18981115 Used at concentrations achieved clinically, imatinib impaired Treg immunosuppressive function and FoxP3 expression but not production of IL-10 and TGF-beta in vitro.
349 18981115 Imatinib significantly reduced the activation of the transcription factors STAT3 and STAT5 in Treg.
350 18981115 Analysis of Treg TCR-induced signaling cascade indicated that imatinib inhibited phosphorylation of ZAP70 and LAT.
351 19009291 Also, anti-inflammatory effects on LPS-stimulated monocytes (TNF-alpha is decreased) and costimulatory effects on anti-CD3 stimulated T cells, (enhanced T cell proliferation and proinflammatory cytokine production) are observed.
352 19009291 Both drugs inhibit IL-2-mediated generation of FOXP3 positive CTLA-4 positive CD25high CD4+ T regulatory cells from PBMCs by upto 50%.
353 19009291 Inhibition of T regulatory cell function was not due to changes in TGF-beta or IL-10 production but was associated with decreased T regulatory cell FOXP3 expression.
354 19009291 Also, anti-inflammatory effects on LPS-stimulated monocytes (TNF-alpha is decreased) and costimulatory effects on anti-CD3 stimulated T cells, (enhanced T cell proliferation and proinflammatory cytokine production) are observed.
355 19009291 Both drugs inhibit IL-2-mediated generation of FOXP3 positive CTLA-4 positive CD25high CD4+ T regulatory cells from PBMCs by upto 50%.
356 19009291 Inhibition of T regulatory cell function was not due to changes in TGF-beta or IL-10 production but was associated with decreased T regulatory cell FOXP3 expression.
357 19028560 A single injection of testosterone on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCRalphabeta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic defeminization/masculinization of thymic (decreased CD4+CD8-TCRalphabeta(high)/CD4-CD8+TCRalphabeta(high) cell ratio) and peripheral blood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio).
358 19028560 In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood.
359 19050244 Mucosal administration of Ag conjugated to cholera toxin B subunit (CTB) can efficiently induce peripheral immunologic tolerance, so-called oral tolerance, associated with development of Foxp3(+)CD25(+)CD4(+) regulatory T (Treg) cells.
360 19050244 B cells from OVA/CTB-treated mice expressed more IL-10 and less CD86 than control B cells.
361 19050244 Adoptive transfer of these cells before parenteral immunization with OVA led to efficient suppression of proliferation and to induction of apoptotic depletion of Ag-specific CD25(-)CD4(+) effector T cells associated with the expansion of Treg cells.
362 19050244 However, also OVA/CTB-treated microMT(-/-) mice could suppress the immune response to parenteral immunization with OVA, which was associated with a strong increase in Foxp3(-)CD4(+) T cells expressing LAP/TGF-beta.
363 19050244 Our results indicate that mucosal tolerance comprises at least two separate pathways: one being B cell dependent and associated with expansion of Treg cells and Treg-mediated suppression and depletion of effector T cells, and one being B cell independent and associated with development of Foxp3(-)LAP(+)TGF-beta(+) regulatory T cells.
364 19050244 Mucosal administration of Ag conjugated to cholera toxin B subunit (CTB) can efficiently induce peripheral immunologic tolerance, so-called oral tolerance, associated with development of Foxp3(+)CD25(+)CD4(+) regulatory T (Treg) cells.
365 19050244 B cells from OVA/CTB-treated mice expressed more IL-10 and less CD86 than control B cells.
366 19050244 Adoptive transfer of these cells before parenteral immunization with OVA led to efficient suppression of proliferation and to induction of apoptotic depletion of Ag-specific CD25(-)CD4(+) effector T cells associated with the expansion of Treg cells.
367 19050244 However, also OVA/CTB-treated microMT(-/-) mice could suppress the immune response to parenteral immunization with OVA, which was associated with a strong increase in Foxp3(-)CD4(+) T cells expressing LAP/TGF-beta.
368 19050244 Our results indicate that mucosal tolerance comprises at least two separate pathways: one being B cell dependent and associated with expansion of Treg cells and Treg-mediated suppression and depletion of effector T cells, and one being B cell independent and associated with development of Foxp3(-)LAP(+)TGF-beta(+) regulatory T cells.
369 19050244 Mucosal administration of Ag conjugated to cholera toxin B subunit (CTB) can efficiently induce peripheral immunologic tolerance, so-called oral tolerance, associated with development of Foxp3(+)CD25(+)CD4(+) regulatory T (Treg) cells.
370 19050244 B cells from OVA/CTB-treated mice expressed more IL-10 and less CD86 than control B cells.
371 19050244 Adoptive transfer of these cells before parenteral immunization with OVA led to efficient suppression of proliferation and to induction of apoptotic depletion of Ag-specific CD25(-)CD4(+) effector T cells associated with the expansion of Treg cells.
372 19050244 However, also OVA/CTB-treated microMT(-/-) mice could suppress the immune response to parenteral immunization with OVA, which was associated with a strong increase in Foxp3(-)CD4(+) T cells expressing LAP/TGF-beta.
373 19050244 Our results indicate that mucosal tolerance comprises at least two separate pathways: one being B cell dependent and associated with expansion of Treg cells and Treg-mediated suppression and depletion of effector T cells, and one being B cell independent and associated with development of Foxp3(-)LAP(+)TGF-beta(+) regulatory T cells.
374 19129927 MUC1-specific T cell responses were difficult to evaluate due to increases in activity of all CD8 and CD4 T cells following each vaccination.
375 19129927 Prior to vaccination, patients entered onto this trial had a significantly higher percentage of FoxP3+CD4+ T cells compared to age matched healthy controls.
376 19153229 In addition to regulating autoimmunity and antitumor immunity, CD4(+) CD25(+) FoxP3(+) natural regulatory T (Treg) cells are global regulators of adaptive immune responses.
377 19191902 Analysis of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response.
378 19191902 At the same time, rBCG induced a CD4(+) CD25(+) Foxp3(+) T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner.
379 19191902 Moreover, suppression of CD4(+) CD25(+) T cells could be adoptively transferred.
380 19191902 The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-beta (TGF-beta)-producing CD4(+) CD25(+) Foxp3(+) regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma.
381 19191902 Analysis of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response.
382 19191902 At the same time, rBCG induced a CD4(+) CD25(+) Foxp3(+) T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner.
383 19191902 Moreover, suppression of CD4(+) CD25(+) T cells could be adoptively transferred.
384 19191902 The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-beta (TGF-beta)-producing CD4(+) CD25(+) Foxp3(+) regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma.
385 19191906 Cytotoxic T-lymphocyte antigen 4 (CTLA-4) uniformly suppresses antigen-specific T cells during chronic infection with bacterial, parasitic or viral pathogens.
386 19191906 Although Foxp3(+) CD4(+) T cells are the predominant CTLA-4-expressing cell type in naïve mice, antigen-specific Foxp3(-) CD4(+) cells upregulate CTLA-4 expression after primary L. monocytogenes infection.
387 19191906 Blockade of CTLA-4 results in increased numbers of L. monocytogenes-specific CD4 and CD8 T cells after primary infection with attenuated L. monocytogenes, and confers more rapid bacterial clearance after secondary challenge with virulent L. monocytogenes.
388 19279333 Here, we showed that CD4(+)CD25(+) regulatory T (T(Reg)) cells play a critical role in tumor-specific CD8(+) T-cell tolerance after transplantation.
389 19279333 Removal of T(Reg) cells from the donor lymphocyte graft did not overcome this tolerance because of rapid conversion of donor CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) T(Reg) cells in recipients after transplantation, and depletion of T(Reg) cells in recipients was necessary for the reversal of tumor-specific tolerance.
390 19302243 Antigenic stimulation with cytochrome P450 2J expressed in mouse hepatocellular carcinoma cells regulates host anti-tumour immunity.
391 19302243 Cytochrome P450 2J subfamily (CYP2J) enzymes expressed in mouse hepatocellular carcinoma (HCC) cells were identified as an antigen recognized by specific CD4(+) T cells and the structure of its T cell epitope was determined by proteomics-based exploration.
392 19302243 Increased frequencies of CD4(+)forkhead box P3 regulatory T cells and CD11b(+)Gr-1(+) myeloid suppressor cells were observed in splenocytes from the continuously immunized mice.
393 19306502 T cell expression of the inhibitory receptor programmed death-1 (PD-1) and inhibition of effector T cells (Teffs) by CD4+Foxp3+Tregs are among the many described mechanisms for achieving a balanced immune response.
394 19306502 In this issue of the JCI, Franceschini et al. extend our understanding of how Tregs are modulated during chronic HCV infection by demonstrating that Treg proliferation is inhibited by PD-1 and that this inhibition is mediated by a potentially novel mechanism involving the prevention of IL-2-driven STAT-5phosphorylation.
395 19340966 Cyclophosphan (CP) administered to mice four times with 24 hours intervals decreased levels of T-, B-, T-regulatory (T-reg CD4/CD25/Foxp3) lymphocytes, increased quantity of cells expressing early activation marker CD25 (assessment after 4 hours).
396 19340966 Levels of CD4, CD25, CD8, and CD19 cells in these groups were already closer to control values that points to the beginning of restoration of some disturbances in mechanisms of immunoregulation.
397 19390618 CD4(+)CD25(+) regulatory T cells (Treg cells) are associated with impaired T cell control of Plasmodium spp infection.
398 19390618 CD4(+)CD25(+)Foxp3(+)CD127(lo) Treg cells were significantly elevated in patients with uncomplicated (UM; n = 17) and severe malaria (SM; n = 16) relative to exposed asymptomatic controls (AC; n = 10).
399 19462377 CTLA-4 is required by CD4+CD25+ Treg to control CD4+ T-cell lymphopenia-induced proliferation.
400 19462377 CTLA-4 is constitutively expressed by CD4(+)CD25(+)Foxp3(+) Treg but its precise role in Treg function is not clear.
401 19462377 We demonstrate that Treg expression of CTLA-4 is essential for Treg control of lymphopenia-induced CD4 T-cell expansion.
402 19462377 Despite IL-10 expression, CTLA-4-deficient Treg were unable to control the expansion of CD4(+) target cells in a lymphopenic environment.
403 19478203 Analyses of splenocytes isolated from 12-week-old mice demonstrated that Alum increased the presence of CD4(+)CD25(+)FoxP3(+) regulatory T cells and downregulated the expression of T cell activation markers CD28 and ICOS in Apoe(-)(/)(-) mice but not in C57BL/6 wild-type mice.
404 19533748 Pretreatment frequency of circulating IL-17+ CD4+ T-cells, but not Tregs, correlates with clinical response to whole-cell vaccination in prostate cancer patients.
405 19533748 Surface expression of the chemokine receptors CCR4 and CCR6 was used to further subdivide IL-17-producing cells into subsets with distinct homing properties.
406 19533748 The frequency of circulating regulatory T-cells (Tregs), defined as CD3(+)CD4(+)CD127(lo)Foxp3(+)CD25(+) was compared in the same patients.
407 19533748 The frequency of CCR4(-)IL-17(+)CD4(+) T-cells prevaccination inversely correlated with time to disease progression (TTP) in 23 prostate cancer patients.
408 19577818 The increased thymic cellularity was accompanied by altered thymocyte differentiation/maturation culminating in increased thymic output of naïve T cells as indicated by elevated levels of both CD4+ and CD8+ RTEs in peripheral blood and spleen.
409 19577818 The changes in T-cell development produced: (i) a disproportional increase in cellularity across thymocyte subsets, so that relative proportions of cells at all maturational stages preceding the CD4+CD8+ T cell receptor (TCR)alphabeta(low) stage were reduced; the relative numbers of CD4+CD8+ TCRalphabeta(low) cells entering positive selection and their immediate CD4+CD8+ TCRalphabeta(high) descendents were increased, while those of the most mature CD4+CD8- and CD4-CD8+ TCRalphabeta(high) cells remained unaltered; (ii) enhanced cell proliferation across all thymocyte subsets and (iii) reduced apoptosis of cells within the CD4+CD8+ thymocyte subset.
410 19577818 The greater number of CD4+CD25+Foxp3+ cells in both thymus and peripheral blood suggested augmented thymic production of these cells.
411 19577818 In addition, an increased CD4+/CD8+ cell ratio was found in the spleen of Ovx rats.
412 19609242 We injected intradermally protamine-stabilized mRNAs coding for Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, and Survivin in 21 metastatic melanoma patients.
413 19609242 Granulocyte macrophage colony-stimulating factor was applied as an adjuvant.
414 19609242 During treatment the frequency of Foxp3+/CD4+ regulatory T cells was significantly decreased upon mRNA vaccination in peripheral blood of the patients in the KLH arm, whereas myeloid suppressor cells (CD11b+HLA-DR lo monocytes) were reduced in the patients not receiving KLH.
415 19658096 All individuals demonstrated stable IFN-gamma, IL-2 and IL-4 ex vivo ELISPOT effector responses against P. falciparum-infected RBC (iRBC) Ag, 28 and 90 days after challenge.
416 19658096 However, infected RBC-specific central memory responses, as measured by IFN-gamma cultured ELISPOT, were low and unstable over time, despite CD4(+) T cells being highly proliferative by CFSE dilution, and showed an inverse relationship to parasite density.
417 19658096 This activity could not be accounted for by the expression of IL-10, TGF-beta, FOXP3 or CTLA-4, but proliferating T cells expressed high levels of CD95, indicating a pro-apoptotic phenotype.
418 19666482 Furthermore, inoculation of killed Leishmania parasites into healed mice led to rapid expansion of IL-10-producing CD4(+)CD25(+)Foxp3(+) T cells in lymph nodes draining the primary infection site.
419 19706340 Naloxone can improve the anti-tumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice.
420 19706340 Tumor and spleen CD4+CD25+Foxp3+ regulatory T lymphocytes, cytotoxic activity of the splenocytes, IFN-gamma and IL-4 secretion were assessed to describe the anti-tumor immune response.
421 19706340 Our findings showed that co-administration of gp96 and naloxone has resulted in a significant reduction in CD4+CD25+Foxp3+ regulatory T cells in the spleen.
422 19706340 Naloxone can improve the anti-tumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice.
423 19706340 Tumor and spleen CD4+CD25+Foxp3+ regulatory T lymphocytes, cytotoxic activity of the splenocytes, IFN-gamma and IL-4 secretion were assessed to describe the anti-tumor immune response.
424 19706340 Our findings showed that co-administration of gp96 and naloxone has resulted in a significant reduction in CD4+CD25+Foxp3+ regulatory T cells in the spleen.
425 19706340 Naloxone can improve the anti-tumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice.
426 19706340 Tumor and spleen CD4+CD25+Foxp3+ regulatory T lymphocytes, cytotoxic activity of the splenocytes, IFN-gamma and IL-4 secretion were assessed to describe the anti-tumor immune response.
427 19706340 Our findings showed that co-administration of gp96 and naloxone has resulted in a significant reduction in CD4+CD25+Foxp3+ regulatory T cells in the spleen.
428 19752238 Furthermore, suppression of T1D was dependent on beta cell-specific IL-10-secreting CD4+ T cells, although the frequency of GAD65-specific FoxP3-expressing CD4+ T cells was also increased in sIA(g7)-pGAD65 dimer vaccinated NOD mice.
429 19767842 The analysis of the inoculation site and draining lymph nodes of the IL-6-/- mice revealed a constitutive reduction in lymphocyte numbers, particularly CD4+ T cells.
430 19767842 Live vaccination resulted in the specific expansion of CD4+Foxp3+ regulatory T cells in the knockout mice, and in a decrease of CD4+ IFN-gamma -producing cells.
431 19768458 Here, we report that a therapeutic whole cell vaccine formulated with IL-2 adsorbed onto aluminum hydroxide as cytokine-depot formulation elicits potent antitumor immunity and induces delayed tumor growth, control of tumor dissemination and longer survival in mice challenged with A20-lymphoma.
432 19768458 Therapeutic vaccination induced higher numbers of tumor's infiltrating lymphocytes (CD4(+) and CD8(+) T cells and NK cells), and the production of IFN-gamma and IL-4 by intratumoral CD4(+) T cells.
433 19768458 Both the A20-derived antigenic material and the IL-2 depot formulation were required for induction of an effective immune response that impacted on cancer progression.
434 19768458 All mice receiving any form of IL-2, either as part of the vaccine or alone as control, showed higher numbers of CD4(+)CD25(+/high)Foxp3(+) regulatory T cells (Treg) in the tumor, which might have a role in tumor progression in these animals.
435 19782714 Because of the central role of regulatory T cells (Tregs) in tumor immunology, we analyzed the frequency and suppressive activity of CD25(+)FoxP3(+) Tregs in 16 patients treated with abagovomab.
436 19782714 During vaccination, mean frequencies of peripheral Treg with a CD4(+)CD25(+)FoxP3(+) CD127(-) phenotype were enhanced but returned to baseline levels in the follow-up phase.
437 19782714 Interestingly, CA-125-specific T-cell activation could not be further improved by Treg depletion in vitro, as CA-125 induced a suppressive CD4(+)CD25(+)FoxP3(+) CD127(-) T cell subset derived from the originally Treg-depleted T-cell fraction.
438 19782714 Because of the central role of regulatory T cells (Tregs) in tumor immunology, we analyzed the frequency and suppressive activity of CD25(+)FoxP3(+) Tregs in 16 patients treated with abagovomab.
439 19782714 During vaccination, mean frequencies of peripheral Treg with a CD4(+)CD25(+)FoxP3(+) CD127(-) phenotype were enhanced but returned to baseline levels in the follow-up phase.
440 19782714 Interestingly, CA-125-specific T-cell activation could not be further improved by Treg depletion in vitro, as CA-125 induced a suppressive CD4(+)CD25(+)FoxP3(+) CD127(-) T cell subset derived from the originally Treg-depleted T-cell fraction.
441 19782714 Because of the central role of regulatory T cells (Tregs) in tumor immunology, we analyzed the frequency and suppressive activity of CD25(+)FoxP3(+) Tregs in 16 patients treated with abagovomab.
442 19782714 During vaccination, mean frequencies of peripheral Treg with a CD4(+)CD25(+)FoxP3(+) CD127(-) phenotype were enhanced but returned to baseline levels in the follow-up phase.
443 19782714 Interestingly, CA-125-specific T-cell activation could not be further improved by Treg depletion in vitro, as CA-125 induced a suppressive CD4(+)CD25(+)FoxP3(+) CD127(-) T cell subset derived from the originally Treg-depleted T-cell fraction.
444 19808957 Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts.
445 19808957 We have previously shown that vaccination of HLA-A2 metastatic melanoma patients with the analogue Melan-A(26-35(A27L)) peptide emulsified in a mineral oil induces ex vivo detectable specific CD8 T cells.
446 19808957 We report that the majority of melanoma patients carry high frequencies of naturally circulating HLA-DQ6-restricted Melan-A-specific CD4 T cells, a high proportion of which express FOXP3 and proliferate poorly in response to the cognate peptide.
447 19808957 In contrast, we found a marked shift to FOXP3-negative CD4 T cells, accompanied by robust CD4 T-cell proliferation upon in vitro stimulation with cognate peptide.
448 19808957 Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts.
449 19808957 We have previously shown that vaccination of HLA-A2 metastatic melanoma patients with the analogue Melan-A(26-35(A27L)) peptide emulsified in a mineral oil induces ex vivo detectable specific CD8 T cells.
450 19808957 We report that the majority of melanoma patients carry high frequencies of naturally circulating HLA-DQ6-restricted Melan-A-specific CD4 T cells, a high proportion of which express FOXP3 and proliferate poorly in response to the cognate peptide.
451 19808957 In contrast, we found a marked shift to FOXP3-negative CD4 T cells, accompanied by robust CD4 T-cell proliferation upon in vitro stimulation with cognate peptide.
452 19923459 Soluble B and T lymphocyte attenuator possesses antitumor effects and facilitates heat shock protein 70 vaccine-triggered antitumor immunity against a murine TC-1 cervical cancer model in vivo.
453 19923459 B and T lymphocyte attenuator (BTLA)-herpesvirus entry mediator (HVEM) signaling coinhibitory pathway is believed to impair antitumor immune competences.
454 19923459 To address this issue, we constructed a eukaryotic expression plasmid (psBTLA) that expressed the extracellular domain of murine BTLA (soluble form of BTLA), which could bind HVEM, the ligand of BTLA, and block BTLA-HVEM interactions.
455 19923459 The data in this study showed that treatment by injection of psBTLA resulted in down-regulation of IL-10 and TGF-beta and promotion of dendritic cell function by increasing the expression of B7-1 and IL-12, but the adaptive antitumor immune responses achieved by psBTLA administration alone were limited and could not eradicate the tumor effectively.
456 19923459 Next, we evaluated the immunotherapeutic efficacy and mechanism of combination therapy of heat shock protein 70 (HSP70) vaccine/psBTLA by using murine TC-1 cervical cancer mice as an ectopic tumor model.
457 19923459 Our in vivo studies revealed that treatment with HSP70 vaccine alone did not lead to satisfactory tumor growth inhibition, whereas cotreatment with psBTLA significantly improved antitumor immunity and compensated the deficiency of HSP70 vaccine by increasing the expression of Th1 cytokines, IL-2, and IFN-gamma and decreasing transcription levels of IL-10, TGF-beta, and Foxp3 in the tumor microenvironment.
458 19952956 Administration of CTX increased the percentage of CD3, CD4, and CD8 cells with the increase in tumors being significantly greater than in spleens, and it also increased the percentage of B cells in spleens and tumors.
459 19952956 Furthermore, CTX dramatically increased the frequency of tumor-infiltrating CD4 and CD8 cells containing interferon gamma, of cells expressing NK1.1, and of cells expressing the dendritic cell markers CD11c, CD80, and CD86, with the greatest increases seen among tumor-infiltrating lymphoid cells (TIL) from mice with small tumors.
460 19952956 Although CTX decreased the percentage of TIL that expressed CD4 or CD8 together with CD25 and FoxP3 and were therefore considered to be regulatory T cells, it increased the frequency of TIL that stained for Gr1/CD11b, a marker for myeloid-derived suppressor cells.
461 20035827 Furthermore, RPEs in vaccinated mice did not augment immunoregulatory responses, as parasite antigen-driven cellular proliferation, production of IL-10, and frequencies of CD4(+)CD25(+)FoxP3(+) regulatory T-cells were not altered by RPEs.
462 20039320 Transient depletion of CD4(+) T cells augments IL-21-based immunotherapy of disseminated neuroblastoma in syngeneic mice.
463 20039320 IL-21 is a member of the IL-2 cytokine family, produced by CD4+ T cells.
464 20039320 Anti-CD25 mAb, indeed, only partially depleted CD4+CD25+FoxP3+ Treg cells, whereas anti-CD4 mAb was more effective in this respect, leading to 90% depletion of Treg cells.
465 20039320 Spleen cells from mice receiving Neuro2a/IL-21 vaccination showed increased expression of IFN-alpha2, -beta1 and -gamma mRNA.
466 20039320 Moreover, mice receiving vaccine therapy alone or vaccine+anti-CD4 mAb showed increased IFN-gamma serum levels and IFN-gamma-producing CD8+ T cells were found in spleen cells.
467 20039320 In conclusion, anti-CD4 mAb potentiated IL-21-based IT by removing Treg cells and/or their precursors and other potentially immune-suppressive CD4+ cell subsets, thus allowing the development of an IL-21-driven CD8+ T cell response, which mediates NB rejection.
468 20053943 Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control.
469 20053943 FOXP3(+)CD8(+) T cells are present at low levels in humans; however, the function of these cells is not known.
470 20053943 In this study, we demonstrate a rapid expansion of CD25(+)FOXP3(+)CD8(+) regulatory T cells (Tregs) in the blood and multiple tissues following a pathogenic SIV infection in rhesus macaques.
471 20053943 These CD8 Tregs expressed molecules associated with immune suppressor function such as CTLA-4 and CD39 and suppressed proliferation of SIV-specific T cells in vitro.
472 20053943 Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control.
473 20053943 FOXP3(+)CD8(+) T cells are present at low levels in humans; however, the function of these cells is not known.
474 20053943 In this study, we demonstrate a rapid expansion of CD25(+)FOXP3(+)CD8(+) regulatory T cells (Tregs) in the blood and multiple tissues following a pathogenic SIV infection in rhesus macaques.
475 20053943 These CD8 Tregs expressed molecules associated with immune suppressor function such as CTLA-4 and CD39 and suppressed proliferation of SIV-specific T cells in vitro.
476 20053943 Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control.
477 20053943 FOXP3(+)CD8(+) T cells are present at low levels in humans; however, the function of these cells is not known.
478 20053943 In this study, we demonstrate a rapid expansion of CD25(+)FOXP3(+)CD8(+) regulatory T cells (Tregs) in the blood and multiple tissues following a pathogenic SIV infection in rhesus macaques.
479 20053943 These CD8 Tregs expressed molecules associated with immune suppressor function such as CTLA-4 and CD39 and suppressed proliferation of SIV-specific T cells in vitro.
480 20063313 Although the frequency of CD4(+)CD25(hi)FOXP3(+) T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminth-uninfected groups: Ag-specific proliferative responses increased upon CD4(+)CD25(hi) T-cell depletion in geohelminth-infected subjects only.
481 20063313 In addition, IFN-gamma production in response to both BCG and parasitized RBC was increased after removal of CD4(+)CD25(hi) T cells.
482 20072623 After in vitro stimulation, spleen cells of immunized mice produce high levels of Th1 cytokines and show a prominent mRNA expression of the Th1 transcription factor T-bet, in detriment of the Th2 transcription factor GATA-3.
483 20072623 Following R. equi challenge, a high H2O2, NO, IL-12, and IFN-gamma content is detected in the organs of immunized mice.
484 20072623 On the other hand, TNF-alpha and IL-4 levels are markedly lower in the organs of vaccinated mice, compared with the non-vaccinated ones.
485 20072623 A greater incidence of CD4+ and CD8+ T cells and B lymphocytes is verified in vaccinated mice.
486 20072623 However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4+CD25+Foxp3+ T cells.
487 20092022 A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study.
488 20092022 We have previously shown in mice that vaccination with three Her-2-peptides representing B-cell epitopes of the extracellular domain of Her-2/neu induces Her-2/neu-specific IgG antibodies with strong anti-tumor activity in vitro and in vivo.
489 20092022 Cellular immune responses, as measured by in vitro production of IL-2, IFN-c, and TNF-a of PBMCs showed a marked increase after vaccination in the majority of vaccinees.
490 20092022 Notably, the number of CD4+CD25+Foxp3+T regulatory cells, which were significantly increased compared to healthy controls prior to vaccination, was markedly reduced following vaccination.
491 20140010 In this study, by analyzing the immune patterns of lymphocytes, we found that the percentage and absolute number of CD4(+)CD25(+)Foxp3(+) regulatory T cells are markedly decreased in naive mice following treatment with LTBI.
492 20140010 On the contrary, the CD4(+)CD44(+)/CD8(+)CD44(+) effect or-memory T cells are greatly increased.
493 20142362 The tolerance correlated with induction of regulatory T cells of the regulatory T type 1 characterized by CD25(-)Foxp3(-)CD4(+) T cells producing IL-10.
494 20142362 In contrast, in IL-10-deficient mice, no peptide-specific tolerance was observed, and these mice exhibited unimpaired CD4(+) T cell responsiveness to recall Ag irrespective of if they were untreated (PBS) or treated i.n. with CTA1R7K-OVA-DD.
495 20168352 Administration of RENCA-H6 inhibited formation and recruitment of Treg cells (CD4+CD25+Foxp3+) and increased maturation of DCs.
496 20168352 RENCA tumors in RENCA-H6- vaccinated animals contained large populations of NK cells and activated CD4+, CD8+ T cells.
497 20168352 In addition, in mice vaccinated with RENCA-H6 cells large population of CD4+ and CD8+ memory cells (CD62Llow) were detected.
498 20308630 Gene expression analysis using tumor-derived RNA demonstrated that imiquimod induced high levels of IL-10 in addition to TNF-alpha and IFN-gamma.
499 20308630 Elevated serum IL-10 appeared to be derived from IL-10 and dual cytokine secreting (IFN-gamma(+) and IL-10(+)) CD4(+) T cells rather than CD4(+)CD25(+)Foxp3(+) T regulatory cells, which were also induced by imiquimod treatment.
500 20308630 Blockade of IL-10, but not TGF-beta, enhanced the antitumor effect of imiquimod by significantly prolonging survival in treated mice.
501 20352042 We tested the hypothesis that therapeutic vaccination against HIV-1 can increase the frequency and suppressive function of regulatory, CD4(+) T cells (Treg), thereby masking enhancement of HIV-1-specific CD8(+) T cell response.
502 20352042 The frequency of CD4(+)CD25(hi)FOXP3(+) Treg in blood was determined prior to and after vaccination in subjects and normal controls.
503 20352042 The increased frequency did not correlate with CD8(+) T cell vaccine response by enzyme linked immunosorbent assay for interferon gamma production.
504 20386464 Increase of circulating CD4+CD25highFoxp3+ regulatory T cells in patients with metastatic renal cell carcinoma during treatment with dendritic cell vaccination and low-dose interleukin-2.
505 20386464 In this study, we analyzed the impact of administration of dendritic cell (DC) vaccination in combination with low-dose interleukin (IL)-2 in patients with metastatic renal cell carcinoma on the frequency of CD4+CD25highFoxp3+ Treg cells in peripheral blood.
506 20386464 Also, in vitro studies showed that coculture of mature DCs, autologous T cells and IL-2 leads to an increase in the number of Treg cells whereas IL-21 does not stimulate the induction of Treg cells.
507 20386464 These findings demonstrate that even low doses of IL-2 in combination with DC vaccination are able to expand CD4+CD25+Foxp3+ Treg cells in vivo in metastatic renal cell carcinoma patients.
508 20394727 Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection.
509 20394727 In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-gamma by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naïve T cells.
510 20394727 Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4(+)CD25(high)Foxp3(+) regulatory T cells.
511 20394727 Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection.
512 20394727 In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-gamma by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naïve T cells.
513 20394727 Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4(+)CD25(high)Foxp3(+) regulatory T cells.
514 20406989 Conjugate vaccines containing human papillomavirus 16 E7 oncoprotein or survivin as a self-TAA had potent therapeutic efficacy against TC-1 cervical and 3LL lung carcinoma tumors, respectively.
515 20406989 Therapeutic efficacy of the vaccines was associated with increased CD4(+) T and CD8(+) T-cell effector and memory responses and higher intratumoral CD8(+) T effector/CD4(+)CD25(+)Foxp3(+) T regulatory cell ratio.
516 20445345 Efficacy of vaccine was tested in immunized HLA-A*0201/H2Dd transgenic mice by measuring the frequency of IFN-gamma secreting cells in the draining lymph nodes, and regulatory T-cell frequencies in the spleen.
517 20445345 Compared with a water-in-oil emulsion vaccine, DPX-0907 enhanced IFN-gamma+CD8+ T cells in vaccine site-draining lymph nodes, as seen by immunofluorescence staining and increased the frequency of IFN-gamma+ lymph node cells as seen by enzyme-linked immunosorbent spot assay.
518 20445345 Notably, while conventional vaccine formulations elicited elevated levels of splenic Foxp3+CD4+ and IL10-secreting T cells, this was not the case for DPX-0907-based vaccines, with treated animals exhibiting normal levels of regulatory T cells.
519 20518016 Recent studies have revealed that Foxp3(+)CD25(+)CD4(+) regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, play critical roles for the control of antitumor immune responses.
520 20544406 Co-administration of GP96 and Her2/neu DNA vaccine in a Her2 breast cancer model.
521 20544406 In this study, animals with Her2-expressing tumors were vaccinated by co-administration of GP96+ Her2/neu DNA vaccines.
522 20544406 Analyses of the immune response, 2 weeks after the last immunization revealed decreased CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (Tregs) at the tumor site and increased IFN-γ/IL-4 level.
523 20547850 The group of patients with smaller lesions displayed stronger and broader vaccine-prompted HPV16-specific proliferative responses with higher IFNgamma (P = 0.0003) and IL-5 (P < 0.0001) levels than patients with large lesions.
524 20547850 In contrast, the patient group with larger lesions mounted higher frequencies of HPV16-specific CD4(+)CD25(+)Foxp3(+) T cells (P = 0.005) and displayed a lower HPV16-specific IFNgamma/IL-10 ratio after vaccination (P < 0.01).
525 20547850 Notably, a high ratio of HPV16-specific vaccine-prompted effector T cells to HPV16-specific CD4(+)CD25(+)Foxp3(+) T cells was predictive of clinical success.
526 20547850 The group of patients with smaller lesions displayed stronger and broader vaccine-prompted HPV16-specific proliferative responses with higher IFNgamma (P = 0.0003) and IL-5 (P < 0.0001) levels than patients with large lesions.
527 20547850 In contrast, the patient group with larger lesions mounted higher frequencies of HPV16-specific CD4(+)CD25(+)Foxp3(+) T cells (P = 0.005) and displayed a lower HPV16-specific IFNgamma/IL-10 ratio after vaccination (P < 0.01).
528 20547850 Notably, a high ratio of HPV16-specific vaccine-prompted effector T cells to HPV16-specific CD4(+)CD25(+)Foxp3(+) T cells was predictive of clinical success.
529 20548030 To focus on the consequences of Treg deficiency confined to the skin, we generated mixed CCR4(KO) FoxP3(KO) bone marrow (CCR4/FoxP3) chimeras in which skin, but not other tissues or central lymphoid organs, lack Treg.
530 20548030 Levels of the antiviral cytokines, type I and II IFNs and IL-12, were reduced, whereas expression of the proinflammatory cytokines, IL-6, IL-10, TGF-beta, and IL-23, was increased.
531 20548030 Importantly, infection of CCR4/FoxP3 chimeras by a noncutaneous route (i.p.) induced immune responses comparable to controls.
532 20548030 To focus on the consequences of Treg deficiency confined to the skin, we generated mixed CCR4(KO) FoxP3(KO) bone marrow (CCR4/FoxP3) chimeras in which skin, but not other tissues or central lymphoid organs, lack Treg.
533 20548030 Levels of the antiviral cytokines, type I and II IFNs and IL-12, were reduced, whereas expression of the proinflammatory cytokines, IL-6, IL-10, TGF-beta, and IL-23, was increased.
534 20548030 Importantly, infection of CCR4/FoxP3 chimeras by a noncutaneous route (i.p.) induced immune responses comparable to controls.
535 20585335 We found that depletion/inactivation of CD4(+)CD25(+) Treg, either by treatment of BALB/c mice with anti-CD25 monoclonal antibodies or by adoptive transfer of CD4(+)CD25(-) T lymphocytes depleted of CD4(+)CD25(+) Treg into nu/nu mice, impaired antibody production after mucosal immunization in the presence of CT.
536 20585335 Conversely, transfer of polyclonal, but not Ag-specific, CD4(+)CD25(+)Foxp3(+) Treg to normal BALB/c mice enhanced CT-induced antibody responses.
537 20585335 Recipients of polyclonal Treg that had been immunized with CT had an increased number of Ag-specific CD4(+) T cells with an activated phenotype (CD44(hi)) in the draining lymph nodes.
538 20600499 In a Flu-vaccination model the role of CD4(+)CD25(+)Foxp3(+) regulatory T-cells (Tregs) and the immune modulation by orally supplied prebiotic oligosaccharides consisting of scGOS/lcFOS/pAOS, were assessed using anti-CD25 (PC61) mediated depletion studies.
539 20600499 In addition, increased T-bet expression of activated CD4(+) T-cells was detected compared to placebo.
540 20635385 Those tumors induced (i) E7-specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non-regressing HPV lesions.
541 20647327 Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hosts.
542 20647327 In this study, we report that approximately 10,000 T cells gene-engineered to express a single-chain IL-12 molecule can be therapeutically effective against established tumors in the absence of exogenous IL-2 and vaccine.
543 20647327 Successful tumor eradication was dependent on a lymphodepleting preconditioning regimen that reduced the number of intratumoral CD4(+) Foxp3(+) T regulatory cells.
544 20827324 As an innovative strategy to circumvent these barriers, vaccine trials to stimulate antigen-specific T-cells polarized toward helper T-cells with a regulatory phenotype (Tregs, CD4+, CD25+, FoxP3+) have also been introduced.
545 20838432 MIG and the regulatory cytokines IL-10 and TGF-β1 correlate with malaria vaccine immunogenicity and efficacy.
546 20838432 The RTS,S/AS02A vaccine offers significant partial efficacy against malaria.mRNA expression of five key cytokines interferon-gamma (IFN-γ), monokine induced by gamma (MIG), interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and forkhead box P3 (FoxP3) in peripheral blood mononuclear cells were measured by real-time RT-PCR before and after vaccination with RTS,S/AS02A and Modified Vaccinia virus Ankara encoding the circumsporozoite protein (MVA-CS) in healthy malaria-naïve adult volunteers.
547 20839259 We, therefore, evaluated the accumulation of regulatory T cells (Tregs, defined as, CD4(+)FoxP3(+)CD25(high)CD127(low)-cells) in blood, ascites, metastases and primary tumours of patients with renal cell carcinoma (RCC), and we explored the effect of neoadjuvant treatment with sorafenib 400 mg bid on intratumoural Tregs in 11 patients with RCC in comparison to 15 nontreated RCC patients.
548 20857491 CD8(+) Foxp3(+) T cells are induced in TIL in regressing tumors of FVB/N mice treated with a GM-CSF secreting HER-2/neu targeted whole cell vaccine.
549 20857491 Interestingly, Foxp3(+) and Foxp3(-) CD8(+) T cells have similar IFN-γ production and antigen-specific degranulation after stimulation with RNEU(420-429) , the immunodominant HER-2/neu (neu) epitope in this model.
550 20857491 CD8(+) Foxp3(+) TILs mark the presence of tumor-rejecting antigen-specific T cells and their accumulation serves as a marker for an effective T cell response.
551 20857491 CD8(+) Foxp3(+) T cells are induced in TIL in regressing tumors of FVB/N mice treated with a GM-CSF secreting HER-2/neu targeted whole cell vaccine.
552 20857491 Interestingly, Foxp3(+) and Foxp3(-) CD8(+) T cells have similar IFN-γ production and antigen-specific degranulation after stimulation with RNEU(420-429) , the immunodominant HER-2/neu (neu) epitope in this model.
553 20857491 CD8(+) Foxp3(+) TILs mark the presence of tumor-rejecting antigen-specific T cells and their accumulation serves as a marker for an effective T cell response.
554 20857491 CD8(+) Foxp3(+) T cells are induced in TIL in regressing tumors of FVB/N mice treated with a GM-CSF secreting HER-2/neu targeted whole cell vaccine.
555 20857491 Interestingly, Foxp3(+) and Foxp3(-) CD8(+) T cells have similar IFN-γ production and antigen-specific degranulation after stimulation with RNEU(420-429) , the immunodominant HER-2/neu (neu) epitope in this model.
556 20857491 CD8(+) Foxp3(+) TILs mark the presence of tumor-rejecting antigen-specific T cells and their accumulation serves as a marker for an effective T cell response.
557 20870946 Using a phage-displayed random peptide library, we identified a 15-mer synthetic peptide, P60, able to bind to forkhead/winged helix transcription factor 3 (FOXP3), a factor required for development and function of Treg.
558 20870946 P60 enters the cells, inhibits FOXP3 nuclear translocation, and reduces its ability to suppress the transcription factors NF-κB and NFAT.
559 20870946 P60 administration to newborn mice induced a lymphoproliferative autoimmune syndrome resembling the reported pathology in scurfy mice lacking functional Foxp3.
560 20870946 Similarly, P60 improved the antiviral efficacy of a recombinant adenovirus expressing NS3 protein from hepatitis C virus.
561 20870946 Functional inhibition of Treg by the FOXP3-inhibitory peptide P60 constitutes a strategy to enhance antitumor and antiviral immunotherapies.
562 20870946 Using a phage-displayed random peptide library, we identified a 15-mer synthetic peptide, P60, able to bind to forkhead/winged helix transcription factor 3 (FOXP3), a factor required for development and function of Treg.
563 20870946 P60 enters the cells, inhibits FOXP3 nuclear translocation, and reduces its ability to suppress the transcription factors NF-κB and NFAT.
564 20870946 P60 administration to newborn mice induced a lymphoproliferative autoimmune syndrome resembling the reported pathology in scurfy mice lacking functional Foxp3.
565 20870946 Similarly, P60 improved the antiviral efficacy of a recombinant adenovirus expressing NS3 protein from hepatitis C virus.
566 20870946 Functional inhibition of Treg by the FOXP3-inhibitory peptide P60 constitutes a strategy to enhance antitumor and antiviral immunotherapies.
567 20870946 Using a phage-displayed random peptide library, we identified a 15-mer synthetic peptide, P60, able to bind to forkhead/winged helix transcription factor 3 (FOXP3), a factor required for development and function of Treg.
568 20870946 P60 enters the cells, inhibits FOXP3 nuclear translocation, and reduces its ability to suppress the transcription factors NF-κB and NFAT.
569 20870946 P60 administration to newborn mice induced a lymphoproliferative autoimmune syndrome resembling the reported pathology in scurfy mice lacking functional Foxp3.
570 20870946 Similarly, P60 improved the antiviral efficacy of a recombinant adenovirus expressing NS3 protein from hepatitis C virus.
571 20870946 Functional inhibition of Treg by the FOXP3-inhibitory peptide P60 constitutes a strategy to enhance antitumor and antiviral immunotherapies.
572 20870946 Using a phage-displayed random peptide library, we identified a 15-mer synthetic peptide, P60, able to bind to forkhead/winged helix transcription factor 3 (FOXP3), a factor required for development and function of Treg.
573 20870946 P60 enters the cells, inhibits FOXP3 nuclear translocation, and reduces its ability to suppress the transcription factors NF-κB and NFAT.
574 20870946 P60 administration to newborn mice induced a lymphoproliferative autoimmune syndrome resembling the reported pathology in scurfy mice lacking functional Foxp3.
575 20870946 Similarly, P60 improved the antiviral efficacy of a recombinant adenovirus expressing NS3 protein from hepatitis C virus.
576 20870946 Functional inhibition of Treg by the FOXP3-inhibitory peptide P60 constitutes a strategy to enhance antitumor and antiviral immunotherapies.
577 20944556 Our data show that EtxB translocates across the nasal epithelium, modulating the expression of interleukin-10 (IL-10) and transforming growth factor-β(1) (TGF-β(1)).
578 20944556 The modulated microenvironment drives an increase in Forkhead box P3 (Foxp3)-positive T cells, predominantly in the CD4(+)CD25(-) subset.
579 20944556 Adoptive transfer experiments showed that enhanced Foxp3 expression was particularly evident in recently activated T cells by concomitant unrelated antigen challenge, and was both TGF-β(1) and IL-10 dependent.
580 20944556 Our data show that EtxB translocates across the nasal epithelium, modulating the expression of interleukin-10 (IL-10) and transforming growth factor-β(1) (TGF-β(1)).
581 20944556 The modulated microenvironment drives an increase in Forkhead box P3 (Foxp3)-positive T cells, predominantly in the CD4(+)CD25(-) subset.
582 20944556 Adoptive transfer experiments showed that enhanced Foxp3 expression was particularly evident in recently activated T cells by concomitant unrelated antigen challenge, and was both TGF-β(1) and IL-10 dependent.
583 20976449 Trends were also observed in analyzing effector:Treg (CD4(+)CD25(+)CD127(-)FoxP3(+)CTLA4(+)) ratio post- versus pre-vaccination with OS versus HPS.
584 21125344 Tonsillar CD4+FOXP3+ T-regulatory cell dynamics in primary EBV infection.
585 21125344 While CD4(+)FOXP3(+) T-regulatory cells (Treg cells) are well accepted to inhibit T-cell responses, it is puzzling why massive expansion of CD8(+) lymphocytes still occurs despite CD4(+)FOXP3(+) Treg cells are localized in tonsils, which are the port of entry of the virus.
586 21125344 Tonsillar CD4+FOXP3+ T-regulatory cell dynamics in primary EBV infection.
587 21125344 While CD4(+)FOXP3(+) T-regulatory cells (Treg cells) are well accepted to inhibit T-cell responses, it is puzzling why massive expansion of CD8(+) lymphocytes still occurs despite CD4(+)FOXP3(+) Treg cells are localized in tonsils, which are the port of entry of the virus.
588 21170302 CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo.
589 21170302 Studies in malaria patients indicate that higher frequencies of peripheral blood CD4(+) Foxp3(+) CD25(+) regulatory T (Treg) cells correlate with increased blood parasitemia.
590 21170302 This protection was entirely dependent upon Foxp3(+) cells and resulted in lower parasite biomass, impaired antigen-specific CD4(+) T and CD8(+) T cell responses that would normally promote parasite tissue sequestration in this model, and reduced recruitment of conventional T cells to the brain.
591 21170302 Furthermore, Foxp3(+) cell-mediated protection was dependent upon CTLA-4 but not IL-10.
592 21335536 Induction of IL-10-producing CD4+ T-cells in chronic periodontitis.
593 21335536 Further, the frequency of RANKL(+)CD4(+) T-cells in GMCs of inflamed gingiva peaked 15 days after infection.
594 21335536 Importantly, the number of Foxp3(+)CD4(+) CD25(+) regulatory T (Treg)-cells was increased only in the experimental group 30 days after infection.
595 21335536 Thus, intracellular cytokine analysis revealed an increased number of IL-10-producing CD4(+) T-cells in inflamed gingiva when compared with the control group.
596 21389872 Aldara treatment was associated with a reduction in the number CD4(+)Foxp3(+) regulatory T cells in the blood and brain tumor site.
597 21389872 Mice treated with Aldara exhibited a generalized lymphopenia in the blood amidst an increase in brain tumor infiltrating CD4(+) and CD8(+) T cells and dendritic cells.
598 21533081 TLR2-dependent induction of IL-10 and Foxp3+ CD25+ CD4+ regulatory T cells prevents effective anti-tumor immunity induced by Pam2 lipopeptides in vivo.
599 21533081 When we investigated the immune suppressive mechanisms, systemic injection of Pam2 lipopeptides induced IL-10 in a TLR2-dependent manner.
600 21533081 The Pam2 lipopeptides increased the frequencies of Foxp3(+)CD4(+) regulatory T (T reg) cells in a TLR2- and IL-10- dependent manner.
601 21533081 TLR2-dependent induction of IL-10 and Foxp3+ CD25+ CD4+ regulatory T cells prevents effective anti-tumor immunity induced by Pam2 lipopeptides in vivo.
602 21533081 When we investigated the immune suppressive mechanisms, systemic injection of Pam2 lipopeptides induced IL-10 in a TLR2-dependent manner.
603 21533081 The Pam2 lipopeptides increased the frequencies of Foxp3(+)CD4(+) regulatory T (T reg) cells in a TLR2- and IL-10- dependent manner.
604 21536741 After physiologically relevant low-dose infection with L. major (1,000 parasites), mice depleted of all Langerin(+) DCs developed significantly smaller ear lesions with decreased parasite loads and a reduced number of CD4(+) Foxp3(+) regulatory T cells (T reg cells) as compared with controls.
605 21554089 Cancer vaccination reprograms regulatory T cells into helper CD4 T cells to promote antitumor CD8 T-cell responses.
606 21554089 It has been recognized that natural CD4(+)Foxp3(+) Tregs could display a phenotypic and functional plasticity in an inflammatory microenvironment.
607 21554089 Sharma et al. demonstrate that in response to vaccines containing antigens, IFA and CpG, a large proportion of Tregs are dedifferentiated into Th1-like effector cells, which coexpress CD40L - a key molecule for CD8 help by licensing dendritic cells.
608 21554089 Collectively, in response to signaling from innate immune cells, Tregs are rapidly reprogrammed into Th1-like effector cells, which are also capable of providing timely help for antigen-specific CD8 T cells in the early phase of activation, when the traditional cognate help from conventional CD4 T cells has not yet became available.
609 21715555 Uncoupling of proliferation and cytokines from suppression within the CD4+CD25+Foxp3+ T-cell compartment in the 1st year of human type 1 diabetes.
610 21795460 Effector T cell responses were increased in the vaccinated mice infected with HN878, but these diminished in number after day 30 of the infections concomitant with increased CD4(+) Foxp3(+) T cells in the lungs, draining lymph nodes, and the spleen.
611 21829534 NY-ESO-1-specific circulating CD4+ T cells in ovarian cancer patients are prevalently T(H)1 type cells undetectable in the CD25+ FOXP3+ Treg compartment.
612 21829534 Spontaneous CD4(+) T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC).
613 21829534 We found that circulating ESO-specific CD4(+) T cells in EOC patients with spontaneous immune responses to the antigen are prevalently T(H)1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive.
614 21829534 ESO tetramer(+) cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25(+)FOXP3(+)Treg.
615 21966415 CD4+FoxP3+ regulatory T cells from Gαi2-/- mice are functionally active in vitro, but do not prevent colitis.
616 22025707 CD4(+)CD25(+)Forkhead box P3 (Foxp3)(+) regulatory T cells (Tregs) control immune responses to self and foreign antigens in secondary lymphoid organs and at tissue sites of inflammation.
617 22025707 CD28 signaling is known to abrogate Treg suppression of IL-2 secretion and proliferation, but our studies show that Treg suppression of IFN-γ during Th1 priming proceeds despite enhanced CD28 signaling.
618 22025707 In vivo, Tregs potently controlled CD4 IFN-γ and CD4 effector cell expansion in the lymph node (four- to fivefold reduction) but not Th1 programming, independent of IL-10.
619 22025707 Tregs additionally reduced CD4 IFN-γ in the inflamed dermis (twofold reduction) dependent on their production of IL-10.
620 22038848 Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4(+) CD25(hi) CD127(low) FoxP3(+) cell (Treg cell) and T lymphocyte activation.
621 22038848 The median proportion of CD4(+) T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4(+) T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latent M. tuberculosis infection (0.14%), or no M. tuberculosis infection (0.32%) (P = 0.005).
622 22049519 Furthermore, the addition of CpG as an adjuvant, or injection of B7H1-blocking or OX40-agonist Abs, further enhanced the therapeutic effects of the vaccine.
623 22049519 Mechanistic studies revealed that DKK1 vaccine elicited a strong DKK1- and tumor-specific CD4+ and CD8+ immune responses, and treatment with B7H1 or OX40 Abs significantly reduced the numbers of IL-10-expressing and Foxp3+ regulatory T cells in vaccinated mice.
624 22130166 Increased antibody levels were also observed to the tumor antigens Melan-A, MAGE-A4, SSX2, and p53.
625 22130166 For peripheral T-cell populations, statistically significant increases in the percent of activated (HLA-DR) CD4 and CD8 T cells with concomitant decreases in naive CD4 and CD8 T cells were observed after ipilimumab treatment.
626 22130166 Increases were also observed in central memory, effector memory, and activated ICOS CD4 T cells, but not in ICOS CD8 T cells or in FoxP3 CD4 regulatory T cells.
627 22138356 LTBSC treatment increased the frequency of CD4(+)FoxP3(+) Treg cells in lymph nodes prior to challenge and in the EAE acute stage.
628 22138356 LTBSC also up-regulated the expression of anti-inflammatory Th2/Th3 cytokines and diminished myelin basic protein-specific Th1 and Th17 cell responses in lymph nodes.
629 22138356 CD4(+)CD25(+) Treg cells from LTBSC treated rats showed stronger suppressive properties than Treg cells from controls in vitro.
630 22139992 Vaccine-induced p53-specific interferon-gamma (IFN-γ)-producing T cells evaluated by IFN-γ ELISPOT were observed in 90% (9/10) and 87.5% (7/8) of evaluable patients after two and four immunizations, respectively.
631 22139992 Cyclophosphamide induced neither a quantitative reduction of Tregs determined by CD4+ FoxP3+ T cell levels nor a demonstrable qualitative difference in Treg function tested in vitro.
632 22139992 Nonetheless, the number of vaccine-induced p53-specific IFN-γ-producing T cells was higher in our study compared to a study in which a similar patient group was treated with p53-SLP monotherapy (p≤0.012).
633 22169715 CD4(+) CD25(+) FoxP3(+) T regulatory cells in subjects responsive or unresponsive to hepatitis B vaccination.
634 22193988 The protective effect of co-administering TGF-β1 siRNA with the DC vaccine was associated with suppression of CD25+ Foxp3+ and CD25+ IL-10+ T cells and enhancement of tumor infiltrating CD4 and CD8 T cells.
635 22221010 The immunization induced ZP3-specific CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg), which suppressed the induction of ZP3-specific delayed-type hypersensitivity in the animals.
636 22250081 With OVA as model Ag, when naive T cells were cocultured in vitro with B cells pretreated with OVA conjugated to CTB (OVA/CTB) Ag-specific CD4(+) Foxp3 regulatory T (Treg) cells increased >50-fold.
637 22250081 These cells effectively suppressed CD25(-)CD4(+) effector T (Teff) cells in secondary cultures.
638 22250081 Likewise, adoptive transfer of B cells pulsed with myelin oligodendrocyte glycoprotein peptide(35-55) (MOGp) conjugated to CTB increased the number of Treg cells, suppressed MOGp-specific T cell proliferation and IL-17 and IFN-γ production, and prevented the development of experimental autoimmune encephalomyelitis.
639 22355381 The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation.
640 22355381 Furthermore, there were an increased percentage of CD4+CD25+Foxp3+T cells in the spleens of neonates.
641 22374980 However, at a late time point after immunization, effector function was reduced to the same level as noncastrated mice and was accompanied by a concomitant amplification in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) following immunization.
642 22506556 In vitro selective depletion of CD4(+)CD25(+) regulatory T-cells from PBMC using anti-tac-SAP.
643 22506556 It has been shown that naturally occurring regulatory T-cells (CD4(+)CD25(+) Foxp3(+) T-cells) have critical roles in tumor invasion and down-regulation of immune response against established tumors.
644 22506556 The aim of this study was to set up an efficient cost-effective protocol to eliminate CD4(+)CD25(+) T-cells-using the immunotoxin anti-tac-SAP.
645 22506556 Flow cytometric analyses were then preformed to analyze expression of CD4, CD25, CD3, CD8, and CD45 surface markers; semi-quantitative fluorescent-PCR was used for the detection of Foxp3 expression before and after anti-tac-SAP treatment.
646 22506556 The results indicated that anti-tac-SAP effectively eliminated CD4(+)CD25(+) T(reg) cells and that 25 µg/dl was the optimal concentration of anti-tac-SAP for selective depletion of these cells.
647 22506556 The results also indicated that this immunotoxin had no non-specific effects on other T-cells, including CD4(+)CD25(-) and CD8(+)CD45(+) T-cells.
648 22506556 Building on the work here, ongoing/future studies with the anti-tac-SAP will focus on functional assessments of the remaining (i.e., non-eliminated) T-cells (i.e., CD8, CD4; using proliferation and peptide sensitization assays) to ascertain if the immunotoxin inadvertently alters the functions of these cells-an untoward outcome.
649 22521604 Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2weeks of age.
650 22521604 CD4(+)FoxP3(+)CD25(+) (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen.
651 22521604 CD8(+)CD223(+) T cells were markedly decreased in the spleens in all offspring at 7weeks of age.
652 22593175 Depletion of CD25(+) FoxP3(+) T(regs) in vivo may promote T cell cancer immunosurveillance, but no strategy to do so in humans while preserving immunity and preventing autoimmunity has been validated.
653 22593175 Robust CD8 and CD4 T cell priming and boosting to all vaccine antigens were observed in the absence of autoimmunity.
654 22678162 Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells.
655 22678162 In this article, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells.
656 22678162 At 6 months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4+ICOS(hi) T cells from 5 ± 2 % pre-vaccination to 23 ± 4 % (p < 0.001), with a concomitant decrease in the frequency of CD4+FoxP3+ T cells (regulatory T cells [Treg]) from 19 ± 6 to 10 ± 5 % (p < 0.05).
657 22678162 ELISpot analysis of CD4+ICOS(hi) sorted T cells demonstrated that following vaccination the cytokines produced by Mam-A-specific T cells switched from IL-10 (78 ± 21 spm pre-vaccination to 32 ± 14 spm 5 months post-vaccine p < 0.001) to IFN-γ (12 ± 6 spm pre-vaccination to 124 ± 31 spm 5 months post-vaccine p < 0.001).
658 22678162 The ratio of CD4+ICOS(hi) T cells to CD4+FoxP3+ T cells increased from 0.37 ± 0.12 before vaccination to 2.3 ± 0.72 (p = 0.021) following vaccination.
659 22678162 Further, these activated CD4+ICOS(hi) T cells induced preferential lysis of human breast cancer cells expressing Mam-A protein.
660 22678162 We conclude that Mam-A cDNA vaccination is associated with specific expansion and activation of CD4+ICOS(hi) T cells, with a concomitant decrease in Treg frequency.
661 22678162 Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells.
662 22678162 In this article, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells.
663 22678162 At 6 months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4+ICOS(hi) T cells from 5 ± 2 % pre-vaccination to 23 ± 4 % (p < 0.001), with a concomitant decrease in the frequency of CD4+FoxP3+ T cells (regulatory T cells [Treg]) from 19 ± 6 to 10 ± 5 % (p < 0.05).
664 22678162 ELISpot analysis of CD4+ICOS(hi) sorted T cells demonstrated that following vaccination the cytokines produced by Mam-A-specific T cells switched from IL-10 (78 ± 21 spm pre-vaccination to 32 ± 14 spm 5 months post-vaccine p < 0.001) to IFN-γ (12 ± 6 spm pre-vaccination to 124 ± 31 spm 5 months post-vaccine p < 0.001).
665 22678162 The ratio of CD4+ICOS(hi) T cells to CD4+FoxP3+ T cells increased from 0.37 ± 0.12 before vaccination to 2.3 ± 0.72 (p = 0.021) following vaccination.
666 22678162 Further, these activated CD4+ICOS(hi) T cells induced preferential lysis of human breast cancer cells expressing Mam-A protein.
667 22678162 We conclude that Mam-A cDNA vaccination is associated with specific expansion and activation of CD4+ICOS(hi) T cells, with a concomitant decrease in Treg frequency.
668 22711885 We also found that human NK cells produce IL-22, which inhibits intracellular growth of M. tuberculosis, and that NK cells lyse M. tuberculosis-expanded CD4(+)CD25(+)FOXP3(+) T regulatory cells (Tregs).
669 22711885 Depletion of NK1.1(+) cells at the time of BCG vaccination increased the number of immunosuppressive Tregs (CD4(+)CD25(hi), 95% Foxp3(+)) after challenge with M. tuberculosis H37Rv, and NK1.1(+) cells lysed expanded but not natural Tregs in BCG-vaccinated mice.
670 22711885 IL-22 at the time of vaccination reversed these effects and enhanced Ag-specific CD4(+) cell responses in BCG-vaccinated mice after challenge with M. tuberculosis H37Rv.
671 22711885 We also found that human NK cells produce IL-22, which inhibits intracellular growth of M. tuberculosis, and that NK cells lyse M. tuberculosis-expanded CD4(+)CD25(+)FOXP3(+) T regulatory cells (Tregs).
672 22711885 Depletion of NK1.1(+) cells at the time of BCG vaccination increased the number of immunosuppressive Tregs (CD4(+)CD25(hi), 95% Foxp3(+)) after challenge with M. tuberculosis H37Rv, and NK1.1(+) cells lysed expanded but not natural Tregs in BCG-vaccinated mice.
673 22711885 IL-22 at the time of vaccination reversed these effects and enhanced Ag-specific CD4(+) cell responses in BCG-vaccinated mice after challenge with M. tuberculosis H37Rv.
674 22723935 The loss of the T memory response following TBI was associated with a relative increase of CD4+CD25+ Foxp3+ expressing T regs, as compared to the CD8+ T effector cells requisite for skin graft rejection.
675 22814407 After challenge, the vaccinated animals displayed markedly reduced lung inflammation and tissue damage, decreased neutrophil infiltration and increased levels of CD4(+)CD25(+)FoxP3(+) regulatory T cells in the lungs compared to non-immunized mice.
676 22860107 Naïve C57BL/6 mice were vaccinated with ESC along with a source of granulocyte macrophage-colony stimulating factor (GM-CSF) in order to provide immunostimulatory adjuvant activity.
677 22860107 Vaccine efficacy was associated with robust tumor-reactive primary and memory CD8(+) T effector responses, Th1 cytokine response, higher intratumoral CD8(+) T effector/CD4(+)CD25(+)Foxp3(+) T regulatory cell ratio, and reduced myeloid derived suppressor cells in the spleen.
678 22871805 FoxP3⁺ regulatory CD4 T cells control the generation of functional CD8 memory.
679 22871805 The FoxP3(+) regulatory CD4 T-cell subset (Treg) is known as a key suppressive component of the immune system.
680 22871805 We find that the Tregs act early, during the expansion phase of primary CD8 effectors, by fine tuning interleukin-2 exposure of CD8 memory precursors.
681 22894960 The CD3(+), CD127(+), CD4(+)CD25(+) and CD4(+)Foxp3(+) cells were increased significantly post vaccination.
682 22894960 The plasma level of the transforming growth factor (TGF-β), but not interleukin (IL)-2, IL-4, IL-5, IL-10, IFN-γ, TNF-α, was also found to increase significantly after vaccination.
683 22908333 ICOS-expressing CD4 T cells induced via TLR4 in the nasal mucosa are capable of inhibiting experimental allergic asthma.
684 22908333 We investigated whether nasal rather than intrapulmonary application of Protollin, a mucosal adjuvant composed of TLR2 and TLR4 ligands, is sufficient to elicit protection against murine allergic lower airway disease.
685 22908333 Inhibition was dependent on TLR4 and was associated with the induction of ICOS in cells of the nasal mucosa and on both CD4+Foxp3+ and CD4+Foxp3- T cells of the draining lymph nodes (LNs), as well as their recruitment to the lungs.
686 22908333 Adoptive transfer of cervical LN CD4+ICOS+, but not CD4+ICOS-, cells inhibited BPEx-induced airway hyperresponsiveness and bronchoalveolar lavage eosinophilia.
687 22908333 Thus, our data indicate that expansion of resident ICOS-expressing CD4+ T cells of the cervical LNs by nasal mucosal TLR4 stimulation may inhibit the development of allergic lower airway disease in mice.
688 22956587 T cell costimulation by TNFR superfamily (TNFRSF)4 and TNFRSF25 in the context of vaccination.
689 22956587 TNFR superfamily (TNFRSF)4 (OX40, CD134) and TNFRSF25 are costimulatory receptors that influence CD4(+) and CD8(+) T cell responses to cognate Ag.
690 22956587 Independently, these receptors have been described to stimulate overlapping functions, including enhanced proliferation and activation for both regulatory T cells (CD4(+)Foxp3(+); Tregs) and conventional T cells (CD4(+)Foxp3(-) or CD8(+)Foxp3(-); Tconvs).
691 22956587 To determine the relative functionality of TNFRSF4 and TNFRSF25 in T cell immunity, the activity of TNFRSF4 and TNFRS25 agonistic Abs was compared in the context of both traditional protein/adjuvant (OVA/aluminum hydroxide) and CD8(+)-specific heat shock protein-based (gp96-Ig) vaccine approaches.
692 22956587 These studies demonstrate that both TNFRSF4 and TNFRSF25 independently and additively costimulate vaccine-induced CD8(+) T cell proliferation following both primary and secondary Ag challenge.
693 22956587 In contrast, the activities of TNFRSF4 and TNFRSF25 were observed to be divergent in the costimulation of CD4(+) T cell immunity.
694 22956587 TNFRSF4 agonists were potent costimulators of OVA/aluminum hydroxide-induced CD4(+) Tconv proliferation, but they only weakly costimulated Treg proliferation and IgG2a production, whereas TNFRSF25 agonists were strong costimulators of Treg proliferation, producers of IgG1, IgG2a, and IgG2b, and weak costimulators of CD4(+) Tconv proliferation.
695 22956587 Interestingly, Ag-specific cellular and humoral responses were uncoupled upon secondary immunization, which was dramatically affected by the presence of TNFRSF4 or TNFRSF25 costimulation.
696 22956587 These studies highlight the overlapping but nonredundant activities of TNFRSF4 and TNFRSF25 in T cell immunity, which may guide the application of receptor agonistic agents as vaccine adjuvants for infectious disease and tumor immunity.
697 23087058 To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC class I and II (MHC-I/II)-restricted epitopes.
698 23087058 Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II-restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status.
699 23087058 In 4 of 15 patients vaccinated with MHC-I/II-loaded DCs and 1 of 14 patients vaccinated with MHC-I-loaded DCs, we detected TAA-specific CD8(+) T cells with maintained IFN-γ production in skin test infiltrating lymphocyte (SKIL) cultures and circulating TAA-specific CD8(+) T cells.
700 23087058 If TAA-specific CD4(+) T-cell responses were detected in SKIL cultures, it coincided with TAA-specific CD8(+) T-cell responses.
701 23087058 In 3 of 13 patients tested, we detected TAA-specific CD4(+)CD25(+)FoxP3(-) T cells with high proliferative capacity and IFN-γ production, indicating that these were not regulatory T cells.
702 23087058 In conclusion, coactivating TAA-specific CD4(+) T-helper cells with DCs pulsed with both MHC class I and II-restricted epitopes augments TAA-specific CD8(+) T-cell responses, contributing to improved clinical responses.
703 23267892 [Prediction of WT1/MUC1 peptide dendritic cell therapy responders by quantification of ex vivo induced mRNA in whole blood].
704 23267892 To challenge this classic problem, we quantified 17 different leukocyte function-associated mRNAs( IFN-γ,TNFSF1, TNFSF2, TNFSF5, IL-10, TGF β,CTLA4, PD1, FOXP3, GMCSF, VEGF, IL-8, CCL8, CXCL3, and IL-2) in whole blood after ex vivo stimulation with 7 different agents(PHA, HAG, zymosan, IFN-γ,rIL-2, aTCR, and picibanil) to activate various subsets of leukocytes.
705 23267892 The clinical outcomes for WT1 peptide-and/or MUC1 peptide-pulsed dendritic cell therapy for advanced cancer (n=26) were CR+PR, 4 cases; SD, 9 cases; and PD, 13 cases.
706 23271806 Recurrent tumors and draining lymph nodes are infiltrated with M2 (CD11b(+)F4/80(hi)CD206(hi) and CD11b(+)F4/80(hi)CD124(hi)) macrophages and CD4(+)Foxp3(+) regulatory T cells.
707 23318147 In the current study, intratumoral (i.t.) injection of recombinant attenuated Salmonella enterica serovar Typhimurium vaccine (RASV) significantly inhibited Her-2/neu-expressing tumor growth.
708 23318147 Although depletion of CD8(+) cells in RASV-treated mice significantly restored tumor growth, the induction of Her-2/neu-specific cytotoxic T lymphocytes (CTLs) was not well correlated with the generation of the anti-tumor effect.
709 23318147 We further investigated whether RASV can modulate immunosuppressive Treg cells, and CD4(+)CD25(+) Foxp3(+) Tregs was significantly reduced in RASV-treated mice.
710 23370281 In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination.
711 23370281 The decrease in IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFβ+% Breg and Treg, respectively.
712 23370281 In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNγ ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%.
713 23370281 In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination.
714 23370281 The decrease in IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFβ+% Breg and Treg, respectively.
715 23370281 In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNγ ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%.
716 23370281 In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination.
717 23370281 The decrease in IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFβ+% Breg and Treg, respectively.
718 23370281 In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNγ ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%.
719 23436617 As immunosuppression by CD4(+) CD25(+) regulatory T (Treg) cells has been linked to the failure of cancer immunotherapy, blocking suppression is therefore critical for successful clinical strategies.
720 23436617 Direct administration of OK-432 into tumor-associated exudate fluids resulted in a reduction of the frequency and suppressive function of CD4(+) CD25(+) Foxp3(+) Treg cells.
721 23436617 Furthermore, when OK-432 was used as an adjuvant of vaccination with HER2 and NY-ESO-1 for esophageal cancer patients, NY-ESO-1-specific CD4(+) T-cell precursors were activated, and NY-ESO-1-specific CD4(+) T cells were detected within the effector/memory T-cell population.
722 23436617 CD4(+) T-cell clones from these patients had high-affinity TCRs and recognized naturally processed NY-ESO-1 protein presented by dendritic cells.
723 23440442 In addition, PA-MSHA treatment increases interleukin-10 levels and promotes the generation of CD4+CD25+Foxp3+ T cells.
724 23453731 IN, but not IR, immunization of mice with 2/6-VLP alone induced antigen-specific IL-10 and IL-17 secreting T cells.
725 23453731 IL-10-, in contrast to IL-17-, secreting T cells did not migrate to the mesenteric lymph nodes (MLN) whereas they were detected in cervical lymph nodes (CLN) and spleen.
726 23453731 With the IN route, the adjuvant allowed to complete this profile with the secretion of IL-2 and IL-4, increased IL-17 secretion and induced antigen specific CD4+CD25+Foxp3+ and Foxp3- T cells in all studied organs (CLN, spleen and MLN) but did not impact on IL-10 secreting T cells.
727 23453731 With the IR route, the adjuvant induced IL-2 and IL-17 secretion but, in contrast to the IN route, did not allow IL-4 production.
728 23492186 AMs were isolated from bronchoalveolar lavage (BAL) fluid from either mice or humans, and cocultured with enriched naive CD4(+)FoxP3(-) T cells.
729 23492186 We show here for the first time that AMs and AM-conditioned media (AM-CM) from mice and humans induced FoxP3 expression in naive CD4(+) T cells in vitro, an outcome that was reversed in part either by inhibiting retinoic acid (RA) binding to its receptor (RAR), or by blocking transforming growth factor (TGF)-β₁ signaling.
730 23492186 A nasal administration of the RAR antagonist reduced the frequencies of CD4(+)FoxP3(+) T cells in the lungs of mice after aerosol challenge with Bordetella pertussis.
731 23492186 AMs were isolated from bronchoalveolar lavage (BAL) fluid from either mice or humans, and cocultured with enriched naive CD4(+)FoxP3(-) T cells.
732 23492186 We show here for the first time that AMs and AM-conditioned media (AM-CM) from mice and humans induced FoxP3 expression in naive CD4(+) T cells in vitro, an outcome that was reversed in part either by inhibiting retinoic acid (RA) binding to its receptor (RAR), or by blocking transforming growth factor (TGF)-β₁ signaling.
733 23492186 A nasal administration of the RAR antagonist reduced the frequencies of CD4(+)FoxP3(+) T cells in the lungs of mice after aerosol challenge with Bordetella pertussis.
734 23502334 Sclareol reduces CD4+ CD25+ FoxP3+ Treg cells in a breast cancer model in vivo.
735 23515135 TSLP-TSLPR (TSLP receptor) interactions also promoted the expansion of colonic Helios(-)Foxp3(+) regulatory T cells, necessary for the control of inappropriate Th17 responses following ASF bacterial colonization.
736 23523770 Most notably CD62L+ and CD25+Foxp3+ counts were shown to be reduced by past studies.
737 23523770 This way, we found that the cell counts obtained after basic lymphocyte differentiation in CD3+CD4+, CD3+CD8+, CD3-CD19+ and CD3-CD56+ were relatively robust for cryopreservation.
738 23523770 However, when further subtyping CD4+ and CD8+ cells, we only found CCR7 and CD45RA to have a relation between fresh and cryopreserved counts, but we could not conclude the same for CD62L.
739 23523770 Also, CD4+CD25+Foxp3+ were shown to be approximately 0.5 times less counted after cryopreservation.
740 23523770 This way, we found that the use of absolute cell counts supported a good one-to-one relation between fresh and cryopreserved counts for all markers except CD62L and CD4+CD25+Foxp3+.
741 23523770 In conclusion, we found no support for the use of CD62L and CD4+CD25+Foxp3+ as markers for calculations on flow cytometric counts from cryopreserved longitudinal datasets.
742 23523770 Most notably CD62L+ and CD25+Foxp3+ counts were shown to be reduced by past studies.
743 23523770 This way, we found that the cell counts obtained after basic lymphocyte differentiation in CD3+CD4+, CD3+CD8+, CD3-CD19+ and CD3-CD56+ were relatively robust for cryopreservation.
744 23523770 However, when further subtyping CD4+ and CD8+ cells, we only found CCR7 and CD45RA to have a relation between fresh and cryopreserved counts, but we could not conclude the same for CD62L.
745 23523770 Also, CD4+CD25+Foxp3+ were shown to be approximately 0.5 times less counted after cryopreservation.
746 23523770 This way, we found that the use of absolute cell counts supported a good one-to-one relation between fresh and cryopreserved counts for all markers except CD62L and CD4+CD25+Foxp3+.
747 23523770 In conclusion, we found no support for the use of CD62L and CD4+CD25+Foxp3+ as markers for calculations on flow cytometric counts from cryopreserved longitudinal datasets.
748 23523770 Most notably CD62L+ and CD25+Foxp3+ counts were shown to be reduced by past studies.
749 23523770 This way, we found that the cell counts obtained after basic lymphocyte differentiation in CD3+CD4+, CD3+CD8+, CD3-CD19+ and CD3-CD56+ were relatively robust for cryopreservation.
750 23523770 However, when further subtyping CD4+ and CD8+ cells, we only found CCR7 and CD45RA to have a relation between fresh and cryopreserved counts, but we could not conclude the same for CD62L.
751 23523770 Also, CD4+CD25+Foxp3+ were shown to be approximately 0.5 times less counted after cryopreservation.
752 23523770 This way, we found that the use of absolute cell counts supported a good one-to-one relation between fresh and cryopreserved counts for all markers except CD62L and CD4+CD25+Foxp3+.
753 23523770 In conclusion, we found no support for the use of CD62L and CD4+CD25+Foxp3+ as markers for calculations on flow cytometric counts from cryopreserved longitudinal datasets.
754 23523770 Most notably CD62L+ and CD25+Foxp3+ counts were shown to be reduced by past studies.
755 23523770 This way, we found that the cell counts obtained after basic lymphocyte differentiation in CD3+CD4+, CD3+CD8+, CD3-CD19+ and CD3-CD56+ were relatively robust for cryopreservation.
756 23523770 However, when further subtyping CD4+ and CD8+ cells, we only found CCR7 and CD45RA to have a relation between fresh and cryopreserved counts, but we could not conclude the same for CD62L.
757 23523770 Also, CD4+CD25+Foxp3+ were shown to be approximately 0.5 times less counted after cryopreservation.
758 23523770 This way, we found that the use of absolute cell counts supported a good one-to-one relation between fresh and cryopreserved counts for all markers except CD62L and CD4+CD25+Foxp3+.
759 23523770 In conclusion, we found no support for the use of CD62L and CD4+CD25+Foxp3+ as markers for calculations on flow cytometric counts from cryopreserved longitudinal datasets.
760 23527092 Our results show that high-dose, myeloablative (MA) TMZ resulted in markedly reduced CD4(+), CD8(+) T-cell and CD4(+)Foxp3(+) TReg counts.
761 23555011 Combined TLR2- and TLR4-activated DC/tumor overcame immune-suppressive effect of TGF-β1 in comparison to those single activated or un-activated DC/tumor as demonstrated by: 1) up-regulation of MHC class II and CD86 expression on DC/tumor; 2) increased fusion efficiency; 3) increased production of fusions derived IL-12p70; 4) activation of CD4(+) and CD8(+) T cells that produce high levels of IFN-γ; 5) augmented induction of CTL activity specific for MUC1; and 6) superior efficacy in inhibiting CD4(+)CD25(+)Foxp3(+) T cell generation.
762 23676757 The study shows that transcription of SEC14L1, GUSB, BPI, CCR7 and TGFβ-1 (all P ≤ 0.05) was downregulated in TB disease compared with uninfected controls, while transcription of RAB33A was downregulated in TB disease compared with both latent TB (P < 0.05) and controls (P < 0.01).
763 23676757 The transcription of CD4, TGFβ-1 (P < 0.01) and the expression of IL-2 (P < 0.01) and IL-13 (P < 0.05) was upregulated in latent TB compared with that in controls.
764 23676757 Using the Least Absolute Shrinkage and Selection Operator (lasso) model, RAB33A alone discriminated between TB disease and latent TB (area under the curve (AUC) 77.5%), whereas a combination of RAB33A, CXCL10, SEC14L1, FOXP3 and TNFRSF1A was effective in discriminating between TB disease and controls (AUC 91.7%).
765 23676757 In conclusion, RAB33A is a potential biomarker for TB disease, whereas CD4, TGFβ-1 and IL-2, IL-13 may identify latent TB in children.
766 23709683 An essential role for C5aR signaling in the optimal induction of a malaria-specific CD4+ T cell response by a whole-killed blood-stage vaccine.
767 23709683 However, the protective efficacy against P. yoelii 17XL challenge is considerably reduced, and the malaria-specific CD4(+) T cell activation and memory T cell differentiation are largely suppressed in the C5aR-deficient (C5aR(-/-)) mice.
768 23709683 An adoptive transfer assay demonstrates that the reduced protection of C5aR(-/-) mice is closely associated with the severely impaired CD4(+) T cell response.
769 23709683 Further study indicates that the defective CD4(+) T cell response in C5aR(-/-) mice is unlikely involved in the expansion of CD4(+)CD25(+)Foxp3(+) T cells, but strongly linked to a defect in dendritic cell (DC) maturation and the ability to allostimulate CD4(+) T cells.
770 23709683 These results demonstrate that C5aR signaling is essential for the optimal induction of the malaria-specific CD4(+) T cell response by the whole-killed parasite vaccine through modulation of DCs function, which provides us with new clues to design an effective blood-stage subunit vaccine and helps us to understand the mechanism by which the T cell response is regulated by the complement system.
771 23725550 Low-dose temozolomide before dendritic-cell vaccination reduces (specifically) CD4+CD25++Foxp3+ regulatory T-cells in advanced melanoma patients.
772 23747993 CD4+ CD31+ recent thymic emigrants in CHD7 haploinsufficiency (CHARGE syndrome): a case.
773 23747993 Thirty two months of flow-cytometric work-up of an athymic (evaluated by four chest X-rays) infant, with a novel CHD7 deletion, demonstrated sparse (<50 cells/mm(3)) but continuous egress of recent thymic emigrants (CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+)) and homeostatic lymphocyte expansion.
774 23747993 Her CD4(+) T cell profile was also characterized by a slightly increased proportion CD4(+) CD25(+) FoxP3(+) T cells.
775 23747993 Since CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+) RTE are reported to be TCR diverse and to contain regulatory T cells, we found it important to report that continuously reduced numbers of CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+) RTE, in the context of CHD7 haploinsufficiency and despite severe lymphopenia, is consistent with an uneventful clinical outcome.
776 23748671 Flow-sorted CD3(+)CD4(+)CD25(+)CD127(low) Tregs were stimulated with anti-CD3/anti-CD28 coated beads and cultured in the presence of IL-2.
777 23748671 The expanded Tregs expressed high levels of FOXP3, CTLA4 and HELIOS compared to conventional T cells and were shown to be highly suppressive.
778 23754615 The Eps8 protein‑pulsed DCs induced significant cytotoxic T lymphocyte (CTL) responses, T-cell proliferation and a higher level of interferon (IFN)-γ in the culture supernatant of the splenocytes ex vivo.
779 23754615 The Eps8 vaccine induced higher CTL responses in the splenocytes of mice vaccinated against the 4T1 cells; the ratio of CD4+/CD8+ T cells was increased in the Eps8 group; and the percentage of CD4+CD25+ FoxP3+ regulatory T (Treg) cells in the Eps8 group was significantly lower compared with that of the PBS group.
780 23790171 ABalb/c mouse model of fibrosarcoma was used and changes in various lymphocyte subpopulations including CD4+, CD8+ and CD4+CD25+Foxp3+ T cells in mice immunized with TL-CD8α+ DCs were studied.
781 23790171 Immunotherapy with TL-CD8α+ DCs significantly enhanced both CD4+ and CD8+ lymphocytes, whereas decreased CD4+CD25+ Foxp3+ regulatory T cells as well as the tumor growth rate.
782 23790171 There was also a decrease in the ratio of regulatory T cells to CD4+ and to CD8+ lymphocytes in both the tumor and spleen tissues as compared to that in the non-immunized control mice.
783 23790171 In conclusion, the current study indicated that TL-CD8α+ DCs can enhance tumor immunity against the fibrosarcoma by enhancing both the CD4+ and CD8+ lymphocytes and reducing regulatory T cells.
784 23790171 ABalb/c mouse model of fibrosarcoma was used and changes in various lymphocyte subpopulations including CD4+, CD8+ and CD4+CD25+Foxp3+ T cells in mice immunized with TL-CD8α+ DCs were studied.
785 23790171 Immunotherapy with TL-CD8α+ DCs significantly enhanced both CD4+ and CD8+ lymphocytes, whereas decreased CD4+CD25+ Foxp3+ regulatory T cells as well as the tumor growth rate.
786 23790171 There was also a decrease in the ratio of regulatory T cells to CD4+ and to CD8+ lymphocytes in both the tumor and spleen tissues as compared to that in the non-immunized control mice.
787 23790171 In conclusion, the current study indicated that TL-CD8α+ DCs can enhance tumor immunity against the fibrosarcoma by enhancing both the CD4+ and CD8+ lymphocytes and reducing regulatory T cells.
788 23844129 Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders.
789 23844129 In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy.
790 23844129 Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A.
791 23845821 Unexpectedly, immunization with the inactivated vaccine only induced a limited immune response and partial protection, which may be due to the decreased activity of dendritic cells and the expansion of CD4+CD25+Foxp3+ regulatory T cells observed in these mice.
792 23874342 CD4(+)Foxp3(+) regulatory T cells (Tregs) have a fundamental role in maintaining immune balance by preventing autoreactivity and immune-mediated pathology.
793 23874845 High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A)-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT) levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6), and number of IFN-γ (+) CD4(+) and IFN-γ (+) CD8(+) T cells in the spleen and liver.
794 23874845 In contrast, CD4(+)CD25(+)Foxp3(+) Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice.
795 23874845 In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation.
796 23874845 High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A)-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT) levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6), and number of IFN-γ (+) CD4(+) and IFN-γ (+) CD8(+) T cells in the spleen and liver.
797 23874845 In contrast, CD4(+)CD25(+)Foxp3(+) Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice.
798 23874845 In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation.
799 23970300 B7-H1 protein vaccine induces protective and therapeutic antitumor responses in SP2/0 myeloma-bearing mice.
800 23970300 The tumor-associated B7-H1 increases apoptosis of antigen-specific T cells through interaction with its receptor PD-1 on CD8+ T cells and contributes to tumor immune evasion.
801 23970300 Vaccination with this modified B7-H1 protein resulted in almost complete protection from SP2/0 tumor challenge and efficiently eliminated pre-established tumors in mice.
802 23970300 In addition, B7-H1 vaccination was able to decrease the percentage of CD4+ Foxp3+ regulatory T cells in tumor-bearing mice and which might improve antitumor immunity.
803 24048897 Recovery of HBsAg-specific responses also correlated with both reduced CD4(+)Foxp3(+) regulatory T cell frequency and an enhanced capacity of effector T cells to overcome inhibition by regulatory T cells.
804 24048897 In conclusion, IL-12-based vaccination therapy may reverse liver-induced immune tolerance toward HBV by restoring systemic HBV-specific CD4(+) T cell responses, eliciting robust hepatic HBV-specific CD8(+) T cell responses, and facilitating the generation of HBsAg-specific humoral immunity; thus, this therapy may become a viable approach to treating patients with chronic hepatitis B.
805 24054944 Although ovariectomy increased thymic output in both 2- and 11-month-old rats, the count of both CD4+ and CD8+ PBLs and splenocytes increased only in the former.
806 24054944 Although ovariectomy affected the total CD4+ count in none of the examined compartments from the 11-month-old rats, it increased CD4+FoxP3+ PBL and splenocyte relative proportions over those in the age-matched controls.
807 24054944 The homeostatic changes within CD8+ splenocyte pool from 11-month-old Ox rats, most likely, reflected the enhanced splenic IL-7 and TGF-β mRNA expression.
808 24089450 Both in vivo and in vitro immune responses toward HBsAg were suppressed by mononuclear cells from HBV-carrier mice, which were CD4(+) Foxp3(-) type 1 regulatory T (Tr1)-like cells producing IL-10.
809 24089450 The purified EGFP(+)CD4(+) T cells (containing Tr1-like cells) from HBV-carrier mice trafficked in higher numbers to DLN in recipient mice after HBsAg vaccination, and subsequently inactivated both Tfh cells and GC B cells via secreting IL-10, resulting in impaired GC formation and anti-HB antibody production.
810 24166949 Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells.
811 24166949 In a series of experiments, we determined that the inability of humanized DR0401.EA(0) mice to elicit specific antibodies was due to expansion and activation of regulatory CD4(+) Foxp3(+) T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions.
812 24177180 Mechanistically, this treatment increased T and B cell responses to reporter antigen immunizations, led to preferential upregulation of OX40 on CD4(+) FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, and increased the antitumor reactivity of T and B cells in patients with melanoma.
813 24244265 Inhibition of CD4+CD25+ regulatory T cell function and conversion into Th1-like effectors by a Toll-like receptor-activated dendritic cell vaccine.
814 24244265 We have previously demonstrated that vaccination with dendritic cells activated with the TLR-4 ligand LPS and IFN-γ promotes an antigen-specific anti-tumor response that prevents tumor recurrence.
815 24244265 The effect is therefore mediated by a soluble factor but was independent of both IL-6 and IL-12.
816 24244265 IFN-γ production was associated with upregulation of the Th1 transcriptional regulator T-bet, and a significant fraction of IFN-γ-producing regulators coexpressed T-bet and FoxP3.
817 24244265 While the effects of the LPS-activated dendritic cell on responder cell proliferation were IL-12 independent, upregulation of T-bet was inhibited by a neutralizing anti-IL-12 antibody.
818 24337378 Using Foxp3(DTR) knock-in mice, we found that Treg-deficient mice had increased Ag-driven production of IFN-γ from both CD4(+) and CD8(+) T cells in the spleen and CNS during the effector phase.
819 24384834 Here, we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4(+)CD25(+)Foxp3(+) regulatory T cells.
820 24426307 CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) are critical for immune homeostasis and tolerance.
821 24426307 Recent studies have targeted the interaction between CCR4 expressed on Tregs and its ligands CCL22 and CCL17 to inhibit transiently the recruitment of Tregs at the site of immunization.
822 24498279 However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice.
823 24498279 Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells.
824 24516200 Furthermore, GX15 increased the apoptosis of regulatory T cells (Tregs), profoundly downregulated FOXP3 and CTLA-4 in a dose-dependent manner, and decreased their suppressive function.
825 24516200 Treating PBMCs obtained from ovarian cancer patients with GX15 also resulted in increased CD8(+):Treg and CD4(+):Treg ratios.
826 24554540 Flow cytometric analysis indicated that the frequencies of both IL-10(+) and IFN-γ(+) CD4(+) Foxp3(+) cells increased significantly in submandibular glands (SMG).
827 24554540 Furthermore, sublingual immunization with rGroEL significantly reduced atherosclerosis lesion formation in the aortic sinus and decreased serum CRP, MCP-1, and ox-LDL levels.
828 24569953 Classically utilized to enumerate lymphocyte subsets, flow cytometric-based assays are increasingly utilized to test immune cell function (e.g., neutrophil oxidative burst, NK cytotoxicity), intracellular cytokine production (e.g., TH17 production), cellular signaling pathways (e.g., phosphor-STAT analysis), and protein expression (e.g., BTK, Foxp3).
829 24587363 Suppression of immunodominant antitumor and antiviral CD8+ T cell responses by indoleamine 2,3-dioxygenase.
830 24587363 Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme known to suppress antitumor CD8(+) T cells (TCD8).
831 24587363 IDO-mediated suppression of these responses was independent of CD4(+)CD25(+)FoxP3(+) regulatory T cells, which remained numerically and functionally intact in IDO(-/-) mice.
832 24605077 TFH cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle.
833 24605077 IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and TFH cell differentiation.
834 24605077 TFH cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells.
835 24605077 The miR-17-92 cluster induces Bcl-6 and TFH cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells.
836 24605077 In addition, follicular regulatory T (TFR) cells are studied as thymus-derived CXCR5(+)PD-1(+)Foxp3(+) Treg cells that play a significant role in limiting the GC response.
837 24611083 The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2-3 months old infants who received BCG vaccination at birth compared to those who did not.
838 24611083 The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants.
839 24633313 Accordingly, following T-cell vaccination the number of IFNγ-producing CD4(+) and CD8(+) T-cells was decreased by 1.6-1.8-fold, which was paralleled by 1.7-fold increases in IL-4-producing CD4(+) T-cells.
840 24633313 In addition, the present study showed 5-7-fold increase in the CD8(+)CD45RO(+)CD62L(-) effector memory T-cells and central memory T-cells (both CD4(+) CD45RO(+)CD62L(+) T-cells and CD8(+)CD45RO(+)CD62L(+) T-cells) in RA patients, as compared with healthy individuals.
841 24633313 We observed significant reduction in CD4(+) and CD8(+) central memory T-cells, as well as reduction in CD8(+) effector memory T-cells in vaccinated patients in the course of the treatment.
842 24633313 We also demonstrated that CD4(+)CD25(+)FoxP3(+) regulatory T-cell levels were significantly up-regulated in the peripheral blood of RA patients following T-cell vaccination.
843 24633313 However, CD4(+)CD25(-)FoxP3(+) Т-cell levels did not significantly change during the entire T-cell vaccination course.
844 24633313 Accordingly, following T-cell vaccination the number of IFNγ-producing CD4(+) and CD8(+) T-cells was decreased by 1.6-1.8-fold, which was paralleled by 1.7-fold increases in IL-4-producing CD4(+) T-cells.
845 24633313 In addition, the present study showed 5-7-fold increase in the CD8(+)CD45RO(+)CD62L(-) effector memory T-cells and central memory T-cells (both CD4(+) CD45RO(+)CD62L(+) T-cells and CD8(+)CD45RO(+)CD62L(+) T-cells) in RA patients, as compared with healthy individuals.
846 24633313 We observed significant reduction in CD4(+) and CD8(+) central memory T-cells, as well as reduction in CD8(+) effector memory T-cells in vaccinated patients in the course of the treatment.
847 24633313 We also demonstrated that CD4(+)CD25(+)FoxP3(+) regulatory T-cell levels were significantly up-regulated in the peripheral blood of RA patients following T-cell vaccination.
848 24633313 However, CD4(+)CD25(-)FoxP3(+) Т-cell levels did not significantly change during the entire T-cell vaccination course.
849 24648995 In this study, we evaluated a TLR9 ligand (CpG oligodeoxynucleotide 1826, CpG) as an adjuvant for a partially protective DNA vaccine encoding a 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST).
850 24648995 Vaccination with pVAX1-Sj26GST in combination with CpG inhibited Treg immunosuppressive function, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2 and IL-6, and decreased CD4+CD8+Foxp3+ expression in vitro, which may contribute to the escape from Treg-mediated suppression during vaccination, allowing expansion of antigen-specific T cells against pathogens.
851 24690994 Transgene IL-6 enhances DC-stimulated CTL responses by counteracting CD4+25+Foxp3+ regulatory T cell suppression via IL-6-induced Foxp3 downregulation.
852 24690994 Moreover, DCOVA/IL-6-stimulated CTL responses were relatively maintained in mice with transfer of CD4+25+Foxp3+ Tr-cells, but significantly reduced when treated with anti-IL-6 antibody.
853 24690994 In addition, we demonstrate that IL-6 down-regulates Foxp3-expression of CD4+25+Foxp3+ Tr-cells in vitro.
854 24690994 Taken together, our results demonstrate that AdV-mediated IL-6 transgene-engineered DC vaccine stimulates potent CTL responses and antitumor immunity by counteracting CD4+25+ Tr immunosuppression via IL-6-induced Foxp3 down-regulation.
855 24690994 Transgene IL-6 enhances DC-stimulated CTL responses by counteracting CD4+25+Foxp3+ regulatory T cell suppression via IL-6-induced Foxp3 downregulation.
856 24690994 Moreover, DCOVA/IL-6-stimulated CTL responses were relatively maintained in mice with transfer of CD4+25+Foxp3+ Tr-cells, but significantly reduced when treated with anti-IL-6 antibody.
857 24690994 In addition, we demonstrate that IL-6 down-regulates Foxp3-expression of CD4+25+Foxp3+ Tr-cells in vitro.
858 24690994 Taken together, our results demonstrate that AdV-mediated IL-6 transgene-engineered DC vaccine stimulates potent CTL responses and antitumor immunity by counteracting CD4+25+ Tr immunosuppression via IL-6-induced Foxp3 down-regulation.
859 24690994 Transgene IL-6 enhances DC-stimulated CTL responses by counteracting CD4+25+Foxp3+ regulatory T cell suppression via IL-6-induced Foxp3 downregulation.
860 24690994 Moreover, DCOVA/IL-6-stimulated CTL responses were relatively maintained in mice with transfer of CD4+25+Foxp3+ Tr-cells, but significantly reduced when treated with anti-IL-6 antibody.
861 24690994 In addition, we demonstrate that IL-6 down-regulates Foxp3-expression of CD4+25+Foxp3+ Tr-cells in vitro.
862 24690994 Taken together, our results demonstrate that AdV-mediated IL-6 transgene-engineered DC vaccine stimulates potent CTL responses and antitumor immunity by counteracting CD4+25+ Tr immunosuppression via IL-6-induced Foxp3 down-regulation.
863 24691994 VISTA is highly expressed on myeloid cells and Foxp3(+)CD4(+) regulatory cells, but not on tumor cells within the tumor microenvironment (TME).
864 24691994 In addition, VISTA blockade impaired the suppressive function and reduced the emergence of tumor-specific Foxp3(+)CD4(+) regulatory T cells.
865 24691994 VISTA is highly expressed on myeloid cells and Foxp3(+)CD4(+) regulatory cells, but not on tumor cells within the tumor microenvironment (TME).
866 24691994 In addition, VISTA blockade impaired the suppressive function and reduced the emergence of tumor-specific Foxp3(+)CD4(+) regulatory T cells.
867 24734217 Dasatinib (DAS) is a potent inhibitor of the BCR-ABL, SRC, c-KIT, PDGFR, and ephrin tyrosine kinases that has demonstrated only modest clinical efficacy in melanoma patients.
868 24734217 The superior efficacy of the combinatorial treatment regimen included a reduction in hypoxic-signaling associated with reduced levels of immunosuppressive CD11b+Gr1+ myeloid-derived suppressor cells (MDSC) and CD4+Foxp3+ regulatory T (Treg) populations in the melanoma microenvironment.
869 24793154 The increased proportion of T regs and high expression of Foxp3 and CTLA-4 on lung cancer cells and tumour infiltrating lymphocytes were observed.
870 24793154 Other components of immune response inhibition and tumour promotion are: Th17 cell population, M2 macrophage polarisation, the presence of myeloid derived suppressor cells (MDSCs) and a significantly elevated concentration of cytokines: TGF-b and IL-10 in the tumour microenvironment.
871 24793154 Lung cancer immunotherapy has two main directions: the first goal is to improve the cytotoxic effect (for example by inhibition of CTLA-4, stimulation of dendritic cell function, inhibition of lymphocyte apoptosis), and the second way is the production of anti-cancer vaccines using known cancer antigens: MAGE A3, MUC1, EGF and TGF-b.
872 24795357 We have shown that a vaccine based on alphavirus replicon particles (VRP) activates strong cellular and humoral immunity to tyrosinase-related protein-2 (TRP2) melanoma antigen, providing prophylactic and therapeutic effects in stringent mouse models.
873 24795357 Here, we report that the immunogenicity and efficacy of this vaccine is increased in combination with either antagonist anti-CTL antigen-4 (CTLA-4) or agonist anti-glucocorticoid-induced TNF family-related gene (GITR) immunomodulatory monoclonal antibodies (mAb).
874 24795357 These mAbs had similar adjuvant effects in priming an adaptive immune response against the vaccine-encoded antigen, augmenting, respectively, approximately 4- and 2-fold the TRP2-specific CD8(+) T-cell response and circulating Abs, compared with the vaccine alone.
875 24795357 Furthermore, while both mAbs increased the frequency of tumor-infiltrating CD8(+) T cells, anti-CTLA-4 mAb also increased the quantity of intratumor CD4(+)Foxp3(-) T cells expressing the negative costimulatory molecule programmed death-1 (PD-1).
876 24795357 They also indicate that tumor-infiltrating CD4(+)Foxp3(-)PD-1(+) T cells may affect the outcome of immunomodulatory treatments.
877 24795357 We have shown that a vaccine based on alphavirus replicon particles (VRP) activates strong cellular and humoral immunity to tyrosinase-related protein-2 (TRP2) melanoma antigen, providing prophylactic and therapeutic effects in stringent mouse models.
878 24795357 Here, we report that the immunogenicity and efficacy of this vaccine is increased in combination with either antagonist anti-CTL antigen-4 (CTLA-4) or agonist anti-glucocorticoid-induced TNF family-related gene (GITR) immunomodulatory monoclonal antibodies (mAb).
879 24795357 These mAbs had similar adjuvant effects in priming an adaptive immune response against the vaccine-encoded antigen, augmenting, respectively, approximately 4- and 2-fold the TRP2-specific CD8(+) T-cell response and circulating Abs, compared with the vaccine alone.
880 24795357 Furthermore, while both mAbs increased the frequency of tumor-infiltrating CD8(+) T cells, anti-CTLA-4 mAb also increased the quantity of intratumor CD4(+)Foxp3(-) T cells expressing the negative costimulatory molecule programmed death-1 (PD-1).
881 24795357 They also indicate that tumor-infiltrating CD4(+)Foxp3(-)PD-1(+) T cells may affect the outcome of immunomodulatory treatments.
882 24830413 Vaccination with irradiated granulocyte macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor cells (GVAX) has been shown to induce therapeutic antitumor immunity.
883 24830413 Indeed, mouse experiments demonstrated that the effective induction of GM-CSF-induced antitumor immunity observed in immunocompetent mice treated with LLC/SeV/GM cells was significantly attenuated when pDC-depleted or IFNα receptor knockout (IFNAR(-/-)) mice were used.
884 24830413 Mechanistically, mice treated with the combined vaccination displayed increased expression levels of CD86, CD9, and Siglec-H, which correlate with an antitumor phenotype, in pDCs, but decreased the ratio of CD4(+)CD25(+)FoxP3(+) regulatory T cells in TDLNs.
885 24830413 Collectively, these findings indicate that the additional use of imiquimod to activate pDCs with type I IFN production, as a positive regulator of T-cell priming, could enhance the immunologic antitumor effects of GVAX therapy, shedding promising light on the understanding and treatment of GM-CSF-based cancer immunotherapy.
886 24860792 IFN-γ, IL17, and IL22 gene expression were up-regulated with an associated increase in their transcription factors, Tbet and RORC, in both treated groups.
887 24860792 TGF-β, IL-10, and FoxP3 were not up-regulated, indicating no activation of regulatory T cells.
888 24872025 Using a highly attenuated Lm dal dat ΔactA strain (LmddA)-based vaccine, we report here that the vector LmddA was sufficient to induce a decrease in the proportion of Tregs by preferentially expanding CD4(+)FoxP3(-) T cells and CD8(+) T cells by a mechanism dependent on and directly mediated by LLO.
889 24872025 These results suggest that LLO may serve as a promising adjuvant by preferentially inducing the expansions of CD4(+)FoxP3(-) T cells and CD8(+) T cells, thus reducing the ratio of Tregs to CD4(+)FoxP3(-) T cells and to CD8(+) T cells favoring immune responses to eradicate tumor.
890 24872025 Using a highly attenuated Lm dal dat ΔactA strain (LmddA)-based vaccine, we report here that the vector LmddA was sufficient to induce a decrease in the proportion of Tregs by preferentially expanding CD4(+)FoxP3(-) T cells and CD8(+) T cells by a mechanism dependent on and directly mediated by LLO.
891 24872025 These results suggest that LLO may serve as a promising adjuvant by preferentially inducing the expansions of CD4(+)FoxP3(-) T cells and CD8(+) T cells, thus reducing the ratio of Tregs to CD4(+)FoxP3(-) T cells and to CD8(+) T cells favoring immune responses to eradicate tumor.
892 24926293 In probing the possible mechanism, we observe that SLA-CpG-DCs vaccination results in the significant decrease in Foxp3(+)GITR(+)CTLA4(+)CD4(+)CD25(+) regulatory T cells (Treg) cell population in Leishmania-infected mice.
893 24926293 Moreover, we demonstrate that a CXC chemokine, IFN-γ-inducible protein 10 (IP-10; CXCL10), has a direct role in the regulation of CD4(+)CD25(+) Treg cells in SLA-CpG-DC-vaccinated parasitized mice as Treg cells isolated from IP-10-depleted vaccinated mice showed significantly increased TGF-β production and suppressive activity.
894 25059463 Survival, proteinuria levels, and CD4(+) Foxp3(+) Treg frequency were monitored during the full experiments.
895 25115805 In these studies CD4(+)CD25(+) T(reg) were depleted using monoclonal antibodies against CD25, which might also interfere with CD25 on non-regulatory T cell populations and would have no effect on Foxp3(+)CD25(-) T(reg).
896 25239487 The splenocytes assay showed oral WH1fungin could suppress T cells proliferation, down-regulate amounts of activated CD8(+) T cells with the production of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and increase CD4(+)CD25(+)FOXP3(+) regulator T cells (Tregs).
897 25252915 Therapeutic efficacy of SA-4-1BBL/MPL was achieved in the absence of detectable toxicity, correlating with enhanced dendritic cell activation, CD8(+) T-cell function, and an increased intratumoral ratio of CD8(+) T effector cells to CD4(+)FoxP3(+) T regulatory cells.
898 25255463 Using depletion experiments, we show that CD4+Foxp3+ regulatory T cells did not mediate the suppression of Ig response during chronic nematode infection.
899 25310804 Serum antibodies were analyzed by ELISA while tissues were used to assess the expression of IgM, IgT, CD4, GATA3, FOXP3, TGF-β and IL-10 genes by quantitative PCR.
900 25310804 This coincided with significant up-regulation of CD4 and GATA3 genes.
901 25310804 CD4 and GATA3 mRNA expressions exhibited a similar pattern to IgT in the hindgut.
902 25362183 We have previously shown in vitro that human DCs treated with glucocorticoids (GCs), IL-10, or TGF-β upregulate the GC-Induced Leucine Zipper protein (GILZ).
903 25362183 GILZ overexpression promotes DC differentiation into regulatory cells that generate IL-10-producing Ag-specific Tregs.
904 25362183 Upon adoptive transfer to wild-type recipient mice, OVA-loaded GILZ(hi) bone marrow-derived DCs induce a reduced activation and proliferation of OVA-specific T cells as compared with control bone marrow-derived DCs, associated with an expansion of thymus-derived CD25(+)Foxp3(+) CD4 T cells.
905 25362183 Transferred OVA-loaded GILZ(hi) DCs produce significantly higher levels of IL-10 and express reduced levels of MHC class II molecules as compared with OVA-loaded control DCs, emphasizing the regulatory phenotype of GILZ(hi) DCs in vivo.
906 25392011 BCG vaccine efficacy waned in C3H/HeOuJ mice, as indicated by reduced expression of gamma interferon (IFN-γ) and increased expressions of interleukin-17 (IL-17), IL-10, and Foxp3 by T cells compared to C3Heb/FeJ mice.
907 25395320 Tumor-infiltrating CD4(+) and CD8(+) T-cells, FOXP3(+) T-regulatory cells, and myeloid-derived suppressor cells were assessed by flow cytometry.
908 25395320 Mammary tumors from TgMMTV-neu contained a lower CD8/CD4 ratio than that of other models (p < 0.05).
909 25395320 MPA-DMBA-induced tumors contained a higher percentage of FOXP3(+) CD4(+) T-cells (p < 0.01) and MDSC (p < 0.001) compared with the other models.
910 25483636 After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3.
911 25483636 Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes.
912 25483636 In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10.
913 25483636 After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3.
914 25483636 Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes.
915 25483636 In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10.
916 25595261 The rat susceptibility to EAE induction, as well as the number of activated CD4+CD134+ lymphocytes retrieved from their spinal cords progressively decreased with aging.
917 25595261 To the contrary, in rats immunized for EAE the number of activated CD4+ splenocytes, i.e., CD4+CD134+, CD4+CD25+FoxP3- and CD4+CD40L+ cells, progressively increased with aging.
918 25595261 This was associated with age-related increase in (i) CD4+ splenocyte surface expression of CD44, the molecule suggested to be involved in limiting emigration of encephalitogenic CD4+ cells from spleen into blood and (ii) frequency of regulatory T cells, including CD4+CD25+FoxP3+ cells, which are also shown to control encephalitogenic cell migration from spleen into the central nervous system.
919 25595261 In favor of expansion of T-regulatory cell pool in aged rats was the greater concentration of IL-10 in unstimulated, Concanavalin A (ConA)- and myelin basic protein (MBP)-stimulated splenocyte cultures from aged rats compared with the corresponding cultures from young ones.
920 25595261 Consistent with the age-related increase in the expression of CD44, which is shown to favor Th1 effector cell survival by interfering with CD95-mediated signaling, the frequency of apoptotic cells among CD4+ splenocytes, despite the greater frequency of CD95+ cells, was diminished in splenocyte cultures from aged compared with young rats.
921 25595261 In addition, in control, as well as in ConA- and MBP-stimulated splenocyte cultures from aged rats, despite of impaired CD4+ cell proliferation, IFN-γ concentrations were greater than in corresponding cultures from young rats.
922 25595261 The diminished CD4+ cell proliferation in response to ConA and MBP in splenocyte cultures from aged compared with young rats could be, at least partly, associated with an enhanced splenic expression of iNOS mRNA in aged rats.
923 25657686 Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.
924 25657686 On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis.
925 25657686 The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period.
926 25657686 Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.
927 25657686 Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.
928 25657686 On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis.
929 25657686 The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period.
930 25657686 Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.
931 25657686 Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.
932 25657686 On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis.
933 25657686 The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period.
934 25657686 Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.
935 25657686 Immunotherapy of rat glioma without accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T cells.
936 25657686 On day 21 after tumor inoculation, all the rats were sacrificed, the brains were harvested for calculation of glioma volume, cytolytic T lymphocyte responses were measured by cytotoxic assay, and the frequency of regulatory T lymphocytes (CD4(+)CD25(+)FOXP3(+)) in the peripheral blood was investigated by flow cytometric analysis.
937 25657686 The frequency of peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes was significantly decreased following the combination therapy, and the rats survived for a longer period.
938 25657686 Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats, boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4(+)CD25(+)FOXP3(+) regulatory T lymphocytes.
939 25775390 Furthermore, sRCPS increased the levels of IL-4, IL-2, and IFN-γ in CD4(+)T cells and the level of IFN-γ in CD8(+)T cells.
940 25775390 In addition, sRCPS enhanced the expression of CD40(+), CD80(+), CD86(+), MHC I and MHC II in dendritic cells (DCs) and upregulated the mRNA levels of MHC I, MHC II. sRCPS downregulated the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells. sRCPS increased both cellular and humoral immune responses by upregulating DC maturation, and suppressing the frequency of Treg cells.
941 25816350 Co-expression of CD25, CD134, CD39 and FoxP3 was used to delineate both antigen-specific Tregs and effectors T cells (Teffs).
942 25816350 Vaccinees who displayed lower levels of HIV-specific CD4+CD134+CD25+CD39+FoxP3+ Tregs responded better to the LIPO-5-DC vaccine.
943 25816350 Co-expression of CD25, CD134, CD39 and FoxP3 was used to delineate both antigen-specific Tregs and effectors T cells (Teffs).
944 25816350 Vaccinees who displayed lower levels of HIV-specific CD4+CD134+CD25+CD39+FoxP3+ Tregs responded better to the LIPO-5-DC vaccine.
945 25851535 ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy.
946 25851535 In this study, we have identified that the ADAP-SKAP55 signaling module reduced CD8(+) CTL cytotoxicity and enhanced PD-1 expression in a Fyn-, Ca(2+)-, and NFATc1-dependent manner.
947 25851535 In DC vaccine-based tumor prevention and therapeutic models, knockout of SKAP55 or ADAP showed a heightened protection from tumor formation or metastases in mice and reduced PD-1 expression in CD8(+) effector cells.
948 25851535 Interestingly, CTLA-4 levels and the percentages of tumor infiltrating CD4(+)Foxp3(+) Tregs remained unchanged.
949 25851535 Furthermore, adoptive transfer of SKAP55-deficient or ADAP-deficient CD8(+) CTLs significantly blocked tumor growth and increased anti-tumor immunity.
950 25851535 Pretreatment of wild-type CD8(+) CTLs with the NFATc1 inhibitor CsA could also downregulate PD-1 expression and enhance anti-tumor therapeutic efficacy.
951 25870600 There were no remaining BCG bacilli, and scarce CD4(+) and Foxp3(+) T cells were determined.
952 25870600 Some CD11c(+) cells proliferated; most of them contained intracellular MART-1 Ag, and some interacted with CD8(+) lymphocytes.
953 25874544 To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1) vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ) and granzyme B (GrB) T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFNγ-effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact), high CD8+CD39+ regulatory T cells (Treg), and low CD19+CD27-CD21- exhausted B cells (Bexhaust).
954 25874544 IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg.
955 25890751 The anti-tumor activity was abrogated completely by depletion of CD8(+) and partially by CD4(+) T lymphocytes.
956 25890751 In addition, the number of IFN-γ-producing CD8(+) T cells in spleen and tumor tissues was significantly increased; but the number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) in tumor tissues was decreased.
957 25924762 In limited studies in cattle, regulatory T cells have been shown to belong to γδ T-cell subsets rather than be CD4 T cells expressing forkhead box protein P3 (FoxP3).
958 25924762 Peripheral blood and spleen mononuclear cells were monitored for MSP1a epitope F2-5B-specfic T-cell proliferative responses and were stained for γδ T-cell subsets or CD4(+) CD25(+) FoxP3(+) T cells before and during infection.
959 25924762 As hypothesized, the induction of T-cell exhaustion occurred only following infection with A. marginale, which did not correlate with an increase in either CD4(+) CD25(+) FoxP3(+) T cells or any γδ T-cell subset examined.
960 25924762 In limited studies in cattle, regulatory T cells have been shown to belong to γδ T-cell subsets rather than be CD4 T cells expressing forkhead box protein P3 (FoxP3).
961 25924762 Peripheral blood and spleen mononuclear cells were monitored for MSP1a epitope F2-5B-specfic T-cell proliferative responses and were stained for γδ T-cell subsets or CD4(+) CD25(+) FoxP3(+) T cells before and during infection.
962 25924762 As hypothesized, the induction of T-cell exhaustion occurred only following infection with A. marginale, which did not correlate with an increase in either CD4(+) CD25(+) FoxP3(+) T cells or any γδ T-cell subset examined.
963 25924762 In limited studies in cattle, regulatory T cells have been shown to belong to γδ T-cell subsets rather than be CD4 T cells expressing forkhead box protein P3 (FoxP3).
964 25924762 Peripheral blood and spleen mononuclear cells were monitored for MSP1a epitope F2-5B-specfic T-cell proliferative responses and were stained for γδ T-cell subsets or CD4(+) CD25(+) FoxP3(+) T cells before and during infection.
965 25924762 As hypothesized, the induction of T-cell exhaustion occurred only following infection with A. marginale, which did not correlate with an increase in either CD4(+) CD25(+) FoxP3(+) T cells or any γδ T-cell subset examined.
966 25934108 Moreover, CVPS increased the expression of IL-2, IFN-γ, and IL-4 in CD4(+) T cells and IFN-γ expression in CD8(+) T cells.
967 25934108 Additionally, CVPS enhanced CD40(+), CD80(+), and CD86(+) expression on DCs.
968 25934108 In contrast, CVPS downregulated TGF-β mRNA expression and the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells.
969 25934108 Taken together, these results indicate that administering CVPS as an adjuvant enhances both cellular and humoral immune responses via the TLR-2 and TLR-4 signalling pathways, thereby promoting DC maturation and suppressing TGF-β expression and Treg frequency.
970 25949867 STAT5 activation, Foxp3 expression, and hnRNPE1 activation mediated by PI3K/Akt signaling were required for Dab2 expression during GM-CSF-derived BMDC development regardless of TGF-β signaling.
971 25949867 Dab2-silencing was accompanied by enhanced IL-12 and IL-6 expression, and an improved capacity of DC for antigen uptake, migration and T cell stimulation, which generated strong CTL in vaccinated mice.
972 26095723 The TLR4 and Foxp3 mRNA and protein levels were determined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively.
973 26095723 The mRNA expression levels of TLR4 and Foxp3 were significantly elevated in the mice that were vaccinated with chitosan as an adjuvant to the H. pylori vaccine, particularly in mice where the H. pylori infection had been eradicated.
974 26095723 The significantly increased TLR4 expression and decreased CD4+CD25+Foxp3+Treg cell number contributed to the immune clearance of the H. pylori infection.
975 26095723 The TLR4 and Foxp3 mRNA and protein levels were determined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively.
976 26095723 The mRNA expression levels of TLR4 and Foxp3 were significantly elevated in the mice that were vaccinated with chitosan as an adjuvant to the H. pylori vaccine, particularly in mice where the H. pylori infection had been eradicated.
977 26095723 The significantly increased TLR4 expression and decreased CD4+CD25+Foxp3+Treg cell number contributed to the immune clearance of the H. pylori infection.
978 26095723 The TLR4 and Foxp3 mRNA and protein levels were determined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively.
979 26095723 The mRNA expression levels of TLR4 and Foxp3 were significantly elevated in the mice that were vaccinated with chitosan as an adjuvant to the H. pylori vaccine, particularly in mice where the H. pylori infection had been eradicated.
980 26095723 The significantly increased TLR4 expression and decreased CD4+CD25+Foxp3+Treg cell number contributed to the immune clearance of the H. pylori infection.
981 26104830 CD4+ FOXP3 Treg numbers were similar between HD and healthy subjects during a 14-day time period post vaccination.
982 26123802 Role of CD4+ Foxp3+ Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii.
983 26123802 Intraperitoneal injection of Mic1.3KO induced a weak and transient influx of CD4(+) Foxp3(+) T regulatory cells followed by recruitment/expansion of CD4(+) Foxp3(-) CD25(+) effector cells and control of the parasite at the site of infection.
984 26123802 In contrast, injection of RH, the wild-type strain from which the vaccinal strain is derived, induced a low CD4(+) Foxp3(+) cell influx and uncontrolled multiplication of the parasites at this local site, followed by death of the mice.
985 26123802 In addition, in vivo Treg induction in RH-infected mice with interleukin-2 (IL-2)/anti-IL-2 complexes induced control of the parasite and a TH1/Treg cytokine response similar to the response after Mic1.3KO vaccination.
986 26123802 Role of CD4+ Foxp3+ Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii.
987 26123802 Intraperitoneal injection of Mic1.3KO induced a weak and transient influx of CD4(+) Foxp3(+) T regulatory cells followed by recruitment/expansion of CD4(+) Foxp3(-) CD25(+) effector cells and control of the parasite at the site of infection.
988 26123802 In contrast, injection of RH, the wild-type strain from which the vaccinal strain is derived, induced a low CD4(+) Foxp3(+) cell influx and uncontrolled multiplication of the parasites at this local site, followed by death of the mice.
989 26123802 In addition, in vivo Treg induction in RH-infected mice with interleukin-2 (IL-2)/anti-IL-2 complexes induced control of the parasite and a TH1/Treg cytokine response similar to the response after Mic1.3KO vaccination.
990 26123802 Role of CD4+ Foxp3+ Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii.
991 26123802 Intraperitoneal injection of Mic1.3KO induced a weak and transient influx of CD4(+) Foxp3(+) T regulatory cells followed by recruitment/expansion of CD4(+) Foxp3(-) CD25(+) effector cells and control of the parasite at the site of infection.
992 26123802 In contrast, injection of RH, the wild-type strain from which the vaccinal strain is derived, induced a low CD4(+) Foxp3(+) cell influx and uncontrolled multiplication of the parasites at this local site, followed by death of the mice.
993 26123802 In addition, in vivo Treg induction in RH-infected mice with interleukin-2 (IL-2)/anti-IL-2 complexes induced control of the parasite and a TH1/Treg cytokine response similar to the response after Mic1.3KO vaccination.
994 26140252 Epstein-Barr virus-induced gene 3 (EBI3) encoded protein can form heterodimers with IL-27P28, and IL-12P35 to form IL-27, and IL-35.
995 26140252 In this study, we evaluated the tumor growth and antitumor T-cell responses in EBI3-deficient mice that lack both IL-27 and IL-35.
996 26140252 Tumors from EBI3-deficient mice contained significantly decreased proportions of CD8+ T cells and increased proportions of CD4+FoxP3+ Treg cells as compared to those from EBI3-intact mice.
997 26140252 Phenotypically, Tregs from EBI3-deficient mice were highly suppressive and produced IL-10 in the tumor microenvironment.
998 26140252 Depletion of Tregs or inactivation of the IL-10 pathway significantly abrogated tumor growth enhancement in Ebi3-/- mice.
999 26140252 Finally, we showed that Ebi3-/- mice administered a melanoma vaccine failed to mount a CD8+ T-cell response and the vaccine failed to confer tumor rejection in EBI3-deficient mice.
1000 26140252 Taken together, these results suggest that Ebi3-/- mice show a phenotype of IL-27-deficiency rather than IL-35-deficiency during anti-tumor T-cell responses.
1001 26270121 Interleukin-28B Plays a Therapeutic Role on Mouse U14 Cervical Cancer Cells by Down-Regulating CD4+CD25+FoxP3+Regulatory T Cells In Vivo.
1002 26297764 TFR are natural regulatory T cells (TREG) that migrate into the follicle and, similar to TFH, upregulate CXCR5, Bcl-6, and PD1.
1003 26297764 In this study, we identified TFR as CD4(+)CD25(+)FOXP3(+)CXCR5(+)PD1(hi)Bcl-6(+) within lymph nodes of rhesus macaques (RM) and confirmed their localization within the GC by immunohistochemistry.
1004 26297764 RNA sequencing showed that TFR exhibit a distinct transcriptional profile with shared features of both TFH and TREG, including intermediate expression of FOXP3, Bcl-6, PRDM1, IL-10, and IL-21.
1005 26310829 In cells from healthy individuals, adenosine hydrolysis decreased CD4(+)CD25(hi) regulatory T cells.
1006 26310829 Addition of 5'-N-ethylcarboxamidoadenosine, an adenosine receptor agonist, significantly decreased CD4(+)CD25(lo) cells, confirming a modulatory role of adenosine acting via adenosine receptors.
1007 26310829 In autologous cocultures of T cells with HIV-1-pulsed dendritic cells, addition of adenosine deaminase led to a significant decrease of HIV-1-induced CD4(+)CD25(hi) forkhead box p3(+) cells and to a significant enhancement of the HIV-1-specific CD4(+) responder T cells.
1008 26310829 An increase in the effector response was confirmed by the enhanced production of CD4(+) and CD8(+) CD25(-)CD45RO(+) memory cell generation and secretion of Th1 cytokines, including IFN-γ and IL-15 and chemokines MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5.
1009 26322930 High postvaccination pH1N1-Th1 responses correlated with baseline high PHA- and pH1N1-IFN-γ ELISpot and circulating CD4(+)CD39(+)% and CD8(+)CD39(+)% Treg, with low CD8(+) cell numbers and CD19(+)FOXP3(+)% Breg, but not with CD4(+) cell numbers or HIV viral load.
1010 26324156 Helios(+)Foxp3(+) and Helios(-)Foxp3(+) Treg cells were unaffected with age.
1011 26324156 Recent thymic emigrants, based on CD31 expression, were decreased among the Helios(+)Foxp3(+), but not the Helios(-)Foxp3(+) cell populations.
1012 26324156 Helios(+)Foxp3(+) and Helios(-)Foxp3(+) Treg cells were unaffected with age.
1013 26324156 Recent thymic emigrants, based on CD31 expression, were decreased among the Helios(+)Foxp3(+), but not the Helios(-)Foxp3(+) cell populations.
1014 26372923 We identified CD3(-)CD20(-)HLA-DR(-)CD14(+)CD33(+)CD11b(+) cells in peripheral blood of healthy rhesus macaques.
1015 26372923 Administration of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte CSF increased their incidence to 5.3% ± 3.4%.
1016 26372923 Freshly isolated or cryopreserved MDSCs from mobilized monkeys incorporated in cultures of anti-CD3- and anti-CD28-stimulated autologous T cells markedly suppressed CD4(+) and CD8(+) T cell proliferation and cytokine secretion (interferon γ, IL-17A).
1017 26372923 Moreover, these MDSCs enhanced CD4(+)CD25(hi)Foxp3(+) regulatory T cell (Treg) expansion while inhibiting proliferation of activated memory T cells and increasing Treg relative to effector and terminally differentiated memory T cells.
1018 26372923 Inhibition of arginase-1, but not inducible nitric oxide synthase activity, partially reversed the inhibitory effect of the MDSCs on CD8(+) T cell proliferation.
1019 26408399 The former reflected a greater suppressive capacity of CD4+CD25+Foxp3+ cells.
1020 26416271 However, in the absence of IL-1β, there was limited proliferation and effector/memory conversion of Ag-specific T cells, depletion of peripheral CD4(+) T cells in hematolymphoid organs, and systemic induction of regulatory Foxp3(+)CD4(+) T cells, as often observed in late-stage HIV disease.
1021 26429981 Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients.
1022 26457200 Aiming to study the influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression of AIRE, FOXP3, H2-Q7 (Qa-2/HLA-G), H2-T23 (Qa-1/HLA-E), H2-Q10, and H2-K1 following immunization with 10,000 LD50 of YFV17D in C57BL/6 and BALB/c mice.
1023 26457200 The YFV17D virus replicated in thymus and induced the expression of H2-Q7 (Qa-2/HLA-G) and H2-T23 (Qa-1/HLA-E) transcripts and repressed the expression of AIRE and FOXP3.
1024 26457200 Expression of H2-T23 (Qa-1/HLA-E) and FOXP3 was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a higher susceptibility to YFV17D infection.
1025 26457200 Aiming to study the influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression of AIRE, FOXP3, H2-Q7 (Qa-2/HLA-G), H2-T23 (Qa-1/HLA-E), H2-Q10, and H2-K1 following immunization with 10,000 LD50 of YFV17D in C57BL/6 and BALB/c mice.
1026 26457200 The YFV17D virus replicated in thymus and induced the expression of H2-Q7 (Qa-2/HLA-G) and H2-T23 (Qa-1/HLA-E) transcripts and repressed the expression of AIRE and FOXP3.
1027 26457200 Expression of H2-T23 (Qa-1/HLA-E) and FOXP3 was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a higher susceptibility to YFV17D infection.
1028 26457200 Aiming to study the influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression of AIRE, FOXP3, H2-Q7 (Qa-2/HLA-G), H2-T23 (Qa-1/HLA-E), H2-Q10, and H2-K1 following immunization with 10,000 LD50 of YFV17D in C57BL/6 and BALB/c mice.
1029 26457200 The YFV17D virus replicated in thymus and induced the expression of H2-Q7 (Qa-2/HLA-G) and H2-T23 (Qa-1/HLA-E) transcripts and repressed the expression of AIRE and FOXP3.
1030 26457200 Expression of H2-T23 (Qa-1/HLA-E) and FOXP3 was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a higher susceptibility to YFV17D infection.
1031 21377510 In addition, the levels of SIV-specific IgA in saliva and plasma were inversely correlated with viral load at euthanasia.
1032 21377510 Interestingly, a marked depletion of CD25(+)FoxP3(+)CD4(+) T cells was observed in the tonsils as well as the intestine of these animals, implying that T regulatory cells may be a major target of SIV infection in infant macaques.