Ignet

Gene Information

Gene symbol: TBX21

Gene name: T-box 21

HGNC ID: 11599

Synonyms: TBLYM, T-bet

Related Genes

#	Gene Symbol	Number of hits
1	BATF	1 hits
2	BCL6	1 hits
3	BDP1	1 hits
4	C8orf4	1 hits
5	CD27	1 hits
6	CD38	1 hits
7	CD4	1 hits
8	CD40	1 hits
9	CD44	1 hits
10	CD80	1 hits
11	CD8A	1 hits
12	CDKN1B	1 hits
13	CXCL10	1 hits
14	CXCR3	1 hits
15	EOMES	1 hits
16	ESRRB	1 hits
17	FOXP3	1 hits
18	GATA3	1 hits
19	GNLY	1 hits
20	GORASP1	1 hits
21	GZMB	1 hits
22	HLA-A	1 hits
23	HLX	1 hits
24	HSPA1A	1 hits
25	IFNG	1 hits
26	IL10	1 hits
27	IL12A	1 hits
28	IL13	1 hits
29	IL15	1 hits
30	IL17A	1 hits
31	IL17C	1 hits
32	IL17D	1 hits
33	IL18BP	1 hits
34	IL2	1 hits
35	IL22	1 hits
36	IL2RA	1 hits
37	IL4	1 hits
38	IL5	1 hits
39	IL6	1 hits
40	IL7R	1 hits
41	IRF6	1 hits
42	IRF8	1 hits
43	KLRG1	1 hits
44	LAMP1	1 hits
45	MLC1	1 hits
46	MYD88	1 hits
47	NFKB1	1 hits
48	PDC	1 hits
49	PPBP	1 hits
50	PRDM1	1 hits
51	PSMD9	1 hits
52	RARA	1 hits
53	RELA	1 hits
54	RORC	1 hits
55	SELL	1 hits
56	SOCS1	1 hits
57	SPN	1 hits
58	STAT1	1 hits
59	T	1 hits
60	TGFA	1 hits
61	TGFB1	1 hits
62	TH1L	1 hits
63	TLR1	1 hits
64	TLR2	1 hits
65	TLR9	1 hits
66	TNF	1 hits

Related Sentences

#	PMID	Sentence
1	12618748	Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions.
2	14685154	However, in EBV-positive Hodgkin's disease (HD) the efficacy of adoptively transferred EBV-specific CTL may be limited by tumor-derived immunosuppressive factors, such as T-cell growth factor (TGF) beta, interleukin (IL)13 and the chemokine TARC.
3	14685154	EBV-specific CTL transduced with a retrovirus vector expressing the p40 and p35 subunits of IL12 as a single molecule (Flexi-IL12), produced IL12 following antigenic stimulation.
4	14685154	This resulted in an elevated production of Th1 cytokines, including interferon gamma and tumor necrosis factor alpha, and a reduction in the Th2 cytokines IL4 and IL5.
5	14685154	Flexi-IL12-transduced CTL resisted the antiproliferative and anticytotoxic effects of exogenous TGFbeta, likely by antagonizing the TGFbeta-induced downregulation of the Th1 transcriptional factor T-bet.
6	15879125	We show, for the first time, that the transcription factor T-bet, which is implicated in IFN-gamma production, is required for the induction of vaccine-induced antiviral immune protection.
7	15879125	This result was associated with an impaired NK cell cytotoxic capacity and NK cell-mediated IFN-gamma production in the T-bet(-/-) mice.
8	15879125	The impaired acquired immune protection in T-bet(-/-) mice was associated with a significantly decreased HSV-2-specific delayed-type hypersensitivity response and a significantly reduced HSV-2-specific IFN-gamma production from CD4(+) T cells.
9	15879125	However, T-bet deficiency did not impair either the IFN-gamma production or the cytotoxic capacity of HSV-2-specific CD8(+) T cells.
10	15879125	We show, for the first time, that the transcription factor T-bet, which is implicated in IFN-gamma production, is required for the induction of vaccine-induced antiviral immune protection.
11	15879125	This result was associated with an impaired NK cell cytotoxic capacity and NK cell-mediated IFN-gamma production in the T-bet(-/-) mice.
12	15879125	The impaired acquired immune protection in T-bet(-/-) mice was associated with a significantly decreased HSV-2-specific delayed-type hypersensitivity response and a significantly reduced HSV-2-specific IFN-gamma production from CD4(+) T cells.
13	15879125	However, T-bet deficiency did not impair either the IFN-gamma production or the cytotoxic capacity of HSV-2-specific CD8(+) T cells.
14	15879125	We show, for the first time, that the transcription factor T-bet, which is implicated in IFN-gamma production, is required for the induction of vaccine-induced antiviral immune protection.
15	15879125	This result was associated with an impaired NK cell cytotoxic capacity and NK cell-mediated IFN-gamma production in the T-bet(-/-) mice.
16	15879125	The impaired acquired immune protection in T-bet(-/-) mice was associated with a significantly decreased HSV-2-specific delayed-type hypersensitivity response and a significantly reduced HSV-2-specific IFN-gamma production from CD4(+) T cells.
17	15879125	However, T-bet deficiency did not impair either the IFN-gamma production or the cytotoxic capacity of HSV-2-specific CD8(+) T cells.
18	15879125	We show, for the first time, that the transcription factor T-bet, which is implicated in IFN-gamma production, is required for the induction of vaccine-induced antiviral immune protection.
19	15879125	This result was associated with an impaired NK cell cytotoxic capacity and NK cell-mediated IFN-gamma production in the T-bet(-/-) mice.
20	15879125	The impaired acquired immune protection in T-bet(-/-) mice was associated with a significantly decreased HSV-2-specific delayed-type hypersensitivity response and a significantly reduced HSV-2-specific IFN-gamma production from CD4(+) T cells.
21	15879125	However, T-bet deficiency did not impair either the IFN-gamma production or the cytotoxic capacity of HSV-2-specific CD8(+) T cells.
22	16188982	The transcription factor T-bet regulates the differentiation of CD4(+) T-helper type 1 (Th1) cells and represses Th2 lineage commitment.
23	16188982	As expected, a significant Th2 shift was observed in CD4(+) T cells of T-bet(-/-) mice.
24	16188982	Furthermore, absence of T-bet impaired VV-specific CD8(+) cytotoxic T-lymphocyte (CTL) function, including cytolytic activity, antiviral cytokine production, and proliferation.
25	16188982	These data reveal that the enhanced susceptibility to VV infection in T-bet(-/-) mice was at least partially due to the Th2 shift of CD4(+) T cells and the diminished function of VV-specific CTLs and NK cells but not due to downregulation of antibody production.
26	16188982	The transcription factor T-bet regulates the differentiation of CD4(+) T-helper type 1 (Th1) cells and represses Th2 lineage commitment.
27	16188982	As expected, a significant Th2 shift was observed in CD4(+) T cells of T-bet(-/-) mice.
28	16188982	Furthermore, absence of T-bet impaired VV-specific CD8(+) cytotoxic T-lymphocyte (CTL) function, including cytolytic activity, antiviral cytokine production, and proliferation.
29	16188982	These data reveal that the enhanced susceptibility to VV infection in T-bet(-/-) mice was at least partially due to the Th2 shift of CD4(+) T cells and the diminished function of VV-specific CTLs and NK cells but not due to downregulation of antibody production.
30	16188982	The transcription factor T-bet regulates the differentiation of CD4(+) T-helper type 1 (Th1) cells and represses Th2 lineage commitment.
31	16188982	As expected, a significant Th2 shift was observed in CD4(+) T cells of T-bet(-/-) mice.
32	16188982	Furthermore, absence of T-bet impaired VV-specific CD8(+) cytotoxic T-lymphocyte (CTL) function, including cytolytic activity, antiviral cytokine production, and proliferation.
33	16188982	These data reveal that the enhanced susceptibility to VV infection in T-bet(-/-) mice was at least partially due to the Th2 shift of CD4(+) T cells and the diminished function of VV-specific CTLs and NK cells but not due to downregulation of antibody production.
34	16188982	The transcription factor T-bet regulates the differentiation of CD4(+) T-helper type 1 (Th1) cells and represses Th2 lineage commitment.
35	16188982	As expected, a significant Th2 shift was observed in CD4(+) T cells of T-bet(-/-) mice.
36	16188982	Furthermore, absence of T-bet impaired VV-specific CD8(+) cytotoxic T-lymphocyte (CTL) function, including cytolytic activity, antiviral cytokine production, and proliferation.
37	16188982	These data reveal that the enhanced susceptibility to VV infection in T-bet(-/-) mice was at least partially due to the Th2 shift of CD4(+) T cells and the diminished function of VV-specific CTLs and NK cells but not due to downregulation of antibody production.
38	16341143	Interestingly, the modified plasmid vaccine predominantly enhanced the type 2 immune responses manifested by an increased IgG1 to IgG2a antibody ratio and a greater induction of GATA-3 and IL-4 mRNA than that of T-bet and IFN-gamma mRNA in spleen cells from vaccinated mice.
39	16341143	In addition, protection against tumor challenge in vaccinated mice showed that there was no significant change in mice survival after in vivo CD8+CTL depletion, indicating that antitumor immunity augmented by plasmid encoding GM-CSF and target PDTRP gene vaccine was dominated by Th2 immune response.
40	17086422	We further showed that the mechanisms involved in the inhibitory effect of C3d3 might be possible due to impairing the function of antigen presenting B lymphocytes and reducing the expression of transcription factors (T-bet and GATA-3) and cytokine IL-4.
41	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.
42	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.
43	17299718	In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4(+)CD25(hi), CTLA-4, and interferon- gamma .
44	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.
45	17299718	There were no significant differences in IL-4 delta 2, IL-10, or TGF- beta receptor-II mRNA expression between groups.
46	17313486	Sequence analysis for potentially candidate genes such as IRF8, MyD88, TLR9, T-bet were performed.
47	17313486	Flow cytometric analysis showed that almost all patient's peripheral B cells had the transitional phenotype (CD24(bright) CD38(bright) CD27(neg)).
48	17313486	Sequence analysis for TLR9, MyD88, IRF8 and T-bet showed no mutations.
49	17313486	Sequence analysis for potentially candidate genes such as IRF8, MyD88, TLR9, T-bet were performed.
50	17313486	Flow cytometric analysis showed that almost all patient's peripheral B cells had the transitional phenotype (CD24(bright) CD38(bright) CD27(neg)).
51	17313486	Sequence analysis for TLR9, MyD88, IRF8 and T-bet showed no mutations.
52	17505023	Induction of a distinct CD8 Tnc17 subset by transforming growth factor-beta and interleukin-6.
53	17505023	Cross-talk between TGF-beta and IL-6 has been shown to direct the differentiation of CD4(+) cells into special IL-17-secreting cells, which are termed Th17 cells.
54	17505023	In this study, we demonstrated that TGF-beta and IL-6 could stimulate CD8(+) cells to differentiate into noncytotoxic, IL-17-producing cells in MLC.
55	17505023	These IL-17-producing CD8(+) cells exhibit a unique granzyme B(-)IFN-gamma(-)IL-10(-) phenotype.
56	17505023	The mRNA level of Th2/T cytotoxic 2 (Tc2) transcription factors GATA3 and Th1/Tc1 transcription factors T-box expressed in T cell (T-bet) as well as its target H2.O-like homeobox (Hlx) is decreased in CD8(+) cells from TGF-beta- and IL-6-treated MLC.
57	17505023	In addition, these CD8(+) cells display a marked up-regulation of retinoic acid-related orphan receptor-gammat, a key IL-17 transcription factor.
58	17505023	These results demonstrate that the existence of an IL-17-producing CD8(+) subset belongs to neither the Tc1 nor the Tc2 subset and can be categorized as a T noncytotoxic 17 (Tnc17) subset.
59	17982028	Temporal and spatial changes of histone 3 K4 dimethylation at the IFN-gamma gene during Th1 and Th2 cell differentiation.
60	17982028	CD4 T cells transgenic for Hlx or infected with T-bet-expressing retrovirus produced IFN-gamma and retained high levels of H3K4me2 even after differentiated under Th2 polarizing conditions, suggesting positive roles of these two factors in maintaining high levels of H3K4me2 at the IFN-gamma gene.
61	17997199	This Th1 shift was supported by an increased T-bet/GATA3 mRNA ratio.
62	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.
63	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.
64	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.
65	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.
66	18390718	The tolerogenic dendritic cell could educate the naive T cells into CD4(+)CD25(-)FoxP3(+) T(REG) cells both in vitro and in vivo.
67	18424713	IL-12 signaling drives CD8+ T cell IFN-gamma production and differentiation of KLRG1+ effector subpopulations during Toxoplasma gondii Infection.
68	18424713	Further phenotypic analysis revealed that the acquisition of KLRG1 among effector subpopulations correlated with the down-regulation of both IL-7R and CD27, suggesting that KLRG1 marks dominant, end-stage effector cells.
69	18424713	Furthermore, IL-12 signaling-dependent T-bet expression was also found to be important for differentiation of KLRG1(+) effectors.
70	18424713	Our results underscore a vital role for IL-12 in not only the induction of IFN-gamma expression but also in the development of heterogeneous subpopulations of effector CD8(+) T cells generated in response to the intracellular parasite T. gondii.
71	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.
72	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.
73	18579694	There were no significant differences in expression of TGF-beta, TGF-beta RII, Foxp3, IFN-gamma, and GATA-3 between the groups.
74	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.
75	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.
76	18579694	There were no significant differences in expression of TGF-beta, TGF-beta RII, Foxp3, IFN-gamma, and GATA-3 between the groups.
77	19285575	Activated macrophages demonstrated upregulation in synthesis of IL-12 and downregulation in IL-10, along with excess IFN gamma production in splenic cells, as evidenced from mRNA analysis.
78	19285575	Induction of such type 1 immunity was further confirmed by expression of type 1 specific transcription factor, T-bet and enhancement of intracellular glutathione content.
79	19285575	Dependence of induced type 1 immune response on the NO release and vice versa was studied by in vitro neutralization of IFN gamma/IL-12 and in vivo inhibition of NO production by methylene blue.
80	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.
81	20072623	Following R. equi challenge, a high H2O2, NO, IL-12, and IFN-gamma content is detected in the organs of immunized mice.
82	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.
83	20072623	A greater incidence of CD4+ and CD8+ T cells and B lymphocytes is verified in vaccinated mice.
84	20072623	However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4+CD25+Foxp3+ T cells.
85	20232336	The mRNA expressions of Th1/Th2 cytokines (IFN-gamma and IL-10) and transcription factors (T-bet and GATA-3) in splenocytes were also markedly up-regulated by 1, compared with the control group immunized with rL-H5 alone (P<0.01 or P<0.001).
86	20434553	Splenocytes were separated for detection of lymphocyte proliferation in responses to concanavalin A (Con A), lipopolysaccharide (LPS) and OVA, and mRNA expression of Th1 cytokines (IFN-gamma and IL-12), Th2 cytokines (IL-10 and IL-5) and transcription factors T-bet/GATA-3 (Th1/Th2 switcher).
87	20434553	In addition, up-regulated T-bet/GATA-3 together with significantly increased mRNA expression of IL-4, IL-10, IFN-gamma and IL-12 by splenocytes, as well as the proliferative responses of splenocytes to Con A, LPS and OVA were observed in paclitaxel-adjuvanted groups.
88	20434553	Incubation of a murine macrophage-like cell line with paclitaxel significantly increased TNF-alpha and -10 released from the cells and expression of microRNAs such as miR-155, miR-147, miR-146a and miR-132.
89	20434553	Splenocytes were separated for detection of lymphocyte proliferation in responses to concanavalin A (Con A), lipopolysaccharide (LPS) and OVA, and mRNA expression of Th1 cytokines (IFN-gamma and IL-12), Th2 cytokines (IL-10 and IL-5) and transcription factors T-bet/GATA-3 (Th1/Th2 switcher).
90	20434553	In addition, up-regulated T-bet/GATA-3 together with significantly increased mRNA expression of IL-4, IL-10, IFN-gamma and IL-12 by splenocytes, as well as the proliferative responses of splenocytes to Con A, LPS and OVA were observed in paclitaxel-adjuvanted groups.
91	20434553	Incubation of a murine macrophage-like cell line with paclitaxel significantly increased TNF-alpha and -10 released from the cells and expression of microRNAs such as miR-155, miR-147, miR-146a and miR-132.
92	20466823	Optimal TLR9 signal converts tolerogenic CD4-8- DCs into immunogenic ones capable of stimulating antitumor immunity via activating CD4+ Th1/Th17 and NK cell responses.
93	20466823	We have demonstrated previously that CD4-8- DCs secreting TGF-beta stimulate CD4+ Tr1 cell responses.
94	20466823	Here, we have assessed whether TLR4 and TLR9 signaling through LPS and CpG stimulation can convert CD4-8- DC-induced tolerance.
95	20466823	CpG-treated, CD4-8- DCOVA-secreting IL-6/IL-15 induced IFN-gamma/IL-17-secreting/T-bet- and ROR-gammat-expressing CD4+ Th1/Th17, whereas LPS-treated CD4-8- DCOVA stimulated IFN-gamma-secreting/T-bet-expressing CD4+ Th1 responses.
96	20466823	CpG-treated, CD4-8- DCOVA-stimulated CD4+ Th1/Th17 cell responses and antitumor immunity were found to be reduced by using neutralizing anti-IL-6, IL-15, and NK1.1 antibodies in wild-type C57BL/6 mice, IL-15R-/- mice for immunization, or CD4-8- (IL-6-/-) DCOVA for immunization in C57BL/6 mice.
97	20466823	Interestingly, in vitro-generated CD4+ Th17 cells significantly enhanced LPS-treated, CD4-8- DCOVA-induced in vivo antitumor immunity via increasing CD8+ CTL responses (P<0.05), although they did not show any direct killing activity against tumor cells in vitro.
98	20466823	Taken together, our data demonstrate an effect of conversion of tolerogenic DCs into immunogenic ones capable of stimulating antitumor immunity via activating CD4+ Th1/Th17 and NK cell responses by optimal CpG signaling, which may advance current understanding of the importance of TLR9 signaling in a DC-based cancer vaccine.
99	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.
100	20600499	In addition, increased T-bet expression of activated CD4(+) T-cells was detected compared to placebo.
101	20696947	Emerging reports reveal that activating Toll-like receptor-2 (TLR2)-MyD88 signals in CD8 T lymphocytes enhances cytokine production and cytotoxicity; however, the signaling pathway remains undefined.
102	20696947	We found that TLR2 engagement on T-cell receptor transgenic CD8 OT-1 T cells increased T-bet transcription factor levels consequently, augmenting effector transcript and protein levels both in vivo and in vitro.
103	20696947	In contrast, TLR2 agonist did not costimulate TLR2(-/-)OT-1 or MyD88(-/-)OT-1 T cells.
104	20696947	Inhibiting mTOR, Akt, or protein kinase C in T cells abolished the costimulatory effects of the TLR2 agonist.
105	20713880	T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8(+) T cells.
106	20713880	T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8(+) T cell differentiation to Tc17 or Tc2 cells.
107	20713880	Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells.
108	20713880	Instead, T-bet and Eomes are crucial for tumor infiltration by CD8(+) T cells.
109	20713880	This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.
110	20713880	T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8(+) T cells.
111	20713880	T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8(+) T cell differentiation to Tc17 or Tc2 cells.
112	20713880	Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells.
113	20713880	Instead, T-bet and Eomes are crucial for tumor infiltration by CD8(+) T cells.
114	20713880	This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.
115	20713880	T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8(+) T cells.
116	20713880	T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8(+) T cell differentiation to Tc17 or Tc2 cells.
117	20713880	Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells.
118	20713880	Instead, T-bet and Eomes are crucial for tumor infiltration by CD8(+) T cells.
119	20713880	This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.
120	20713880	T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8(+) T cells.
121	20713880	T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8(+) T cell differentiation to Tc17 or Tc2 cells.
122	20713880	Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells.
123	20713880	Instead, T-bet and Eomes are crucial for tumor infiltration by CD8(+) T cells.
124	20713880	This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.
125	20855629	IFN-{gamma} produced by CD8 T cells induces T-bet-dependent and -independent class switching in B cells in responses to alum-precipitated protein vaccine.
126	20855629	These findings led us to question whether adoptive transfer of antigen-specific CD8 T cells alters the characteristic CD4 Th2 response to alum proteins and the switching pattern in responding B cells.
127	20855629	To this end, WT mice given transgenic ovalbumin (OVA)-specific CD4 (OTII) or CD8 (OTI) T cells, or both, were immunized with alum-precipitated OVA.
128	20855629	The transcription factor T-bet is required in B cells for IFN-γ-dependent switching to IgG2a.
129	20855629	IFN-{gamma} produced by CD8 T cells induces T-bet-dependent and -independent class switching in B cells in responses to alum-precipitated protein vaccine.
130	20855629	These findings led us to question whether adoptive transfer of antigen-specific CD8 T cells alters the characteristic CD4 Th2 response to alum proteins and the switching pattern in responding B cells.
131	20855629	To this end, WT mice given transgenic ovalbumin (OVA)-specific CD4 (OTII) or CD8 (OTI) T cells, or both, were immunized with alum-precipitated OVA.
132	20855629	The transcription factor T-bet is required in B cells for IFN-γ-dependent switching to IgG2a.
133	21039472	Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii.
134	21039472	It is widely accepted that antibodies and CD4 T cells play critical roles in the immune response during the blood stage of malaria, whereas the role of CD8 T cells remains controversial.
135	21039472	Here, we show that both CD8 and CD4 T cells robustly responded to an acute self-limiting blood-stage infection with Plasmodium yoelii.
136	21039472	Similar to antigen-specific T cells, both CD8 and CD4 T cells showed dynamic expression of the surface proteins interleukin (IL)-7R and programmed death-1 (PD-1).
137	21039472	Additionally, activated CD8 T cells showed differences in the expression of Killer cell lectin-like receptor G1, L-selectin and B cell lymphoma-2 and produced granzyme B, indicating cytotoxic activity, and the initially high expression of T-box transcription factor TBX21 in malaria-activated CD4 T cells indicated an early T helper type 1 (Th1)-skewed immune response.
138	21039472	Our data demonstrate that blood-stage malaria infection results in a striking T-cell response and that activated CD8 and CD4 T cells have phenotypic and functional characteristics that are consistent with conventional antigen-specific effector and memory T cells.
139	21039472	Therefore, a better understanding of the CD8 and CD4 T-cell response induced by blood-stage infection may prove to be essential in the development of a vaccine that targets the erythrocytic stage of the malarial parasite.
140	21079691	We found that the Th1 subset dominated the UGT, as IFN-γ and T-bet mRNA expression were high, while GATA-3 was low following genital infection with C. trachomatis serovar D.
141	21079691	By contrast, IL-10 and GATA-3 mRNA dominated the LGT, suggesting the presence of Th2 cells.
142	21289306	Importantly, we demonstrate that correlative to memory responses, perioperative immunotherapy increases the formation of tumor-infiltrating and tumor-reactive CD8(+) T cells expressing low levels of the transcription factor T-bet, defined as memory precursor effector cells.
143	21565243	Quantitative RT-PCR revealed genes encoding IFN-γ, IL-17, IL-22, T-bet, RORC, and granulysin were up-regulated in PBMC stimulated with live Map three months post infection compared to the response of PBMC pre-infection.
144	21642544	In naive CD4 T cells, IFN-γ production only occurred after sustained Ag activation and was associated with high expression of the T-bet transcription factor required for Th1 differentiation and with T-bet binding to the IFN-γ promoter as assessed by chromatin immunoprecipitation analysis.
145	21642544	By contrast, immediate IFN-γ production by Ag-stimulated memory CD4 T cells occurred in the absence of significant nuclear T-bet expression or T-bet engagement on the IFN-γ promoter.
146	21642544	In naive CD4 T cells, IFN-γ production only occurred after sustained Ag activation and was associated with high expression of the T-bet transcription factor required for Th1 differentiation and with T-bet binding to the IFN-γ promoter as assessed by chromatin immunoprecipitation analysis.
147	21642544	By contrast, immediate IFN-γ production by Ag-stimulated memory CD4 T cells occurred in the absence of significant nuclear T-bet expression or T-bet engagement on the IFN-γ promoter.
148	21674481	In Plasmodium berghei ANKA (PbA)-infected C57BL/6 mice, CD4(+) T cells controlled parasite numbers poorly, instead providing early help to pathogenic CD8(+) T cells.
149	21674481	IFN-I substantially inhibited CD4(+) T-bet(+) T-cell-derived IFN-γ production, and prevented this emerging Th1 response from controlling parasites.
150	21717068	The number of T-bet(+) TILs correlates with better survival of esophageal cancer patients.
151	21717068	Using well-defined mouse models, we have further shown that T-bet and Eomes are both required for the adaptive anti-tumor immunity by regulating T-cell trafficking into the tumor tissue and their effector functions inside the tumor microenvironment.
152	21717068	In order to gain further insight into the tumor immune microenvironment in the upper GI cancer, we have also studied expression levels of co-inhibitory molecules such as B7-H1/PD-L1 and B7-H4 in tissue specimens of esophageal and gastric cancers.
153	21717068	The number of CD3(+) and CD8(+) TILs correlates inversely with expression levels of B7-H4 in samples from esophageal cancer, supporting a role of active immune suppression by inhibitory B7 molecules in the tumor microenvironment.
154	21717068	In addition, TILs show functional exhaustion and express high levels of PD-1 and Tim-3.
155	21717068	Future tumor vaccine design should combine blockade of B7 inhibitory molecules and enhancement of T-bet and Eomes levels within the tumor microenvironment.
156	21717068	The number of T-bet(+) TILs correlates with better survival of esophageal cancer patients.
157	21717068	Using well-defined mouse models, we have further shown that T-bet and Eomes are both required for the adaptive anti-tumor immunity by regulating T-cell trafficking into the tumor tissue and their effector functions inside the tumor microenvironment.
158	21717068	In order to gain further insight into the tumor immune microenvironment in the upper GI cancer, we have also studied expression levels of co-inhibitory molecules such as B7-H1/PD-L1 and B7-H4 in tissue specimens of esophageal and gastric cancers.
159	21717068	The number of CD3(+) and CD8(+) TILs correlates inversely with expression levels of B7-H4 in samples from esophageal cancer, supporting a role of active immune suppression by inhibitory B7 molecules in the tumor microenvironment.
160	21717068	In addition, TILs show functional exhaustion and express high levels of PD-1 and Tim-3.
161	21717068	Future tumor vaccine design should combine blockade of B7 inhibitory molecules and enhancement of T-bet and Eomes levels within the tumor microenvironment.
162	21717068	The number of T-bet(+) TILs correlates with better survival of esophageal cancer patients.
163	21717068	Using well-defined mouse models, we have further shown that T-bet and Eomes are both required for the adaptive anti-tumor immunity by regulating T-cell trafficking into the tumor tissue and their effector functions inside the tumor microenvironment.
164	21717068	In order to gain further insight into the tumor immune microenvironment in the upper GI cancer, we have also studied expression levels of co-inhibitory molecules such as B7-H1/PD-L1 and B7-H4 in tissue specimens of esophageal and gastric cancers.
165	21717068	The number of CD3(+) and CD8(+) TILs correlates inversely with expression levels of B7-H4 in samples from esophageal cancer, supporting a role of active immune suppression by inhibitory B7 molecules in the tumor microenvironment.
166	21717068	In addition, TILs show functional exhaustion and express high levels of PD-1 and Tim-3.
167	21717068	Future tumor vaccine design should combine blockade of B7 inhibitory molecules and enhancement of T-bet and Eomes levels within the tumor microenvironment.
168	22275868	These included IFN-γ, IL-6, IL-12Rβ2, T-bet, SOCS-1, and IL-18bp.
169	22552442	We found that pcDNA3.1-T-bet-Ag85B not only induced evidently higher IgG2a antibody responses, but also increased the production of interferon-γ (IFN-γ) and interleukin (IL)-2 with the concomitant repression of IL-4 and IL-10 compared with pcDNA3.1-Ag85B alone or the empty vector.
170	22575167	The latter correlated with a marked increase in lung infiltration of IFN-γ- and IL-17-producing CD4(+) T cells.
171	22575167	Elevated expression of T-bet and RORc transcription factors in ΔT-EP67-vaccinated mice indicated the promotion of Th1 and Th17 cell differentiation.
172	22942184	T-box transcription factors T-bet (Tbx21) and Eomesodermin (Eomes) are critical players in CD8(+) cytotoxic T lymphocyte effector function and differentiation, but how the expression of these transcription factors is regulated remains poorly defined.
173	22942184	Here we show that dominant T cells directed toward human CMV, expressing significantly higher levels of T-bet with graded loss of Eomes expression (T-bet(hi)Eomes(hi/lo)), are more efficient in recognizing endogenously processed peptide-major histocompatibility complexes (pMHC) compared with subdominant virus-specific T cells expressing lower levels of T-bet and high levels of Eomes (T-bet(int)Eomes(hi)).
174	22942184	Paradoxically, the T-bet(hi)Eomes(hi/lo) dominant populations that efficiently recognized endogenous antigen demonstrated lower intrinsic avidity for pMHC, whereas T-bet(int)Eomes(hi) subdominant populations were characterized by higher pMHC avidity and less efficient recognition of virus-infected cells.
175	22942184	Importantly, differential endogenous viral antigen recognition by CMV-specific CD8(+) T cells also correlated with the differentiation status and expression of perforin, granzyme B and K.
176	22942184	Furthermore, we demonstrate that the expression of T-bet correlates with clonal expansion, differentiation status, and expression of perforin, granzyme B and K in antigen-specific T cells.
177	22942184	T-box transcription factors T-bet (Tbx21) and Eomesodermin (Eomes) are critical players in CD8(+) cytotoxic T lymphocyte effector function and differentiation, but how the expression of these transcription factors is regulated remains poorly defined.
178	22942184	Here we show that dominant T cells directed toward human CMV, expressing significantly higher levels of T-bet with graded loss of Eomes expression (T-bet(hi)Eomes(hi/lo)), are more efficient in recognizing endogenously processed peptide-major histocompatibility complexes (pMHC) compared with subdominant virus-specific T cells expressing lower levels of T-bet and high levels of Eomes (T-bet(int)Eomes(hi)).
179	22942184	Paradoxically, the T-bet(hi)Eomes(hi/lo) dominant populations that efficiently recognized endogenous antigen demonstrated lower intrinsic avidity for pMHC, whereas T-bet(int)Eomes(hi) subdominant populations were characterized by higher pMHC avidity and less efficient recognition of virus-infected cells.
180	22942184	Importantly, differential endogenous viral antigen recognition by CMV-specific CD8(+) T cells also correlated with the differentiation status and expression of perforin, granzyme B and K.
181	22942184	Furthermore, we demonstrate that the expression of T-bet correlates with clonal expansion, differentiation status, and expression of perforin, granzyme B and K in antigen-specific T cells.
182	22942184	T-box transcription factors T-bet (Tbx21) and Eomesodermin (Eomes) are critical players in CD8(+) cytotoxic T lymphocyte effector function and differentiation, but how the expression of these transcription factors is regulated remains poorly defined.
183	22942184	Here we show that dominant T cells directed toward human CMV, expressing significantly higher levels of T-bet with graded loss of Eomes expression (T-bet(hi)Eomes(hi/lo)), are more efficient in recognizing endogenously processed peptide-major histocompatibility complexes (pMHC) compared with subdominant virus-specific T cells expressing lower levels of T-bet and high levels of Eomes (T-bet(int)Eomes(hi)).
184	22942184	Paradoxically, the T-bet(hi)Eomes(hi/lo) dominant populations that efficiently recognized endogenous antigen demonstrated lower intrinsic avidity for pMHC, whereas T-bet(int)Eomes(hi) subdominant populations were characterized by higher pMHC avidity and less efficient recognition of virus-infected cells.
185	22942184	Importantly, differential endogenous viral antigen recognition by CMV-specific CD8(+) T cells also correlated with the differentiation status and expression of perforin, granzyme B and K.
186	22942184	Furthermore, we demonstrate that the expression of T-bet correlates with clonal expansion, differentiation status, and expression of perforin, granzyme B and K in antigen-specific T cells.
187	22942184	T-box transcription factors T-bet (Tbx21) and Eomesodermin (Eomes) are critical players in CD8(+) cytotoxic T lymphocyte effector function and differentiation, but how the expression of these transcription factors is regulated remains poorly defined.
188	22942184	Here we show that dominant T cells directed toward human CMV, expressing significantly higher levels of T-bet with graded loss of Eomes expression (T-bet(hi)Eomes(hi/lo)), are more efficient in recognizing endogenously processed peptide-major histocompatibility complexes (pMHC) compared with subdominant virus-specific T cells expressing lower levels of T-bet and high levels of Eomes (T-bet(int)Eomes(hi)).
189	22942184	Paradoxically, the T-bet(hi)Eomes(hi/lo) dominant populations that efficiently recognized endogenous antigen demonstrated lower intrinsic avidity for pMHC, whereas T-bet(int)Eomes(hi) subdominant populations were characterized by higher pMHC avidity and less efficient recognition of virus-infected cells.
190	22942184	Importantly, differential endogenous viral antigen recognition by CMV-specific CD8(+) T cells also correlated with the differentiation status and expression of perforin, granzyme B and K.
191	22942184	Furthermore, we demonstrate that the expression of T-bet correlates with clonal expansion, differentiation status, and expression of perforin, granzyme B and K in antigen-specific T cells.
192	23065152	CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines.
193	23065152	This happens when CD8 T cells are recruited into CD4 T cell-dependent B-cell responses.
194	23065152	Ovalbumin-specific CD4 T cells (OTII) were transferred alone or with ovalbumin-specific CD8 T cells (OTI) and the response to subcutaneous alum-precipitated ovalbumin was followed in the draining lymph nodes.
195	23065152	Up-regulation of CXCR3 by GC B cells and AFCs and their migration toward its ligand CXCL10 are shown to depend on B cells' intrinsic T-bet, a transcription factor downstream of the IFN-γR signaling.
196	23065152	CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines.
197	23065152	This happens when CD8 T cells are recruited into CD4 T cell-dependent B-cell responses.
198	23065152	Ovalbumin-specific CD4 T cells (OTII) were transferred alone or with ovalbumin-specific CD8 T cells (OTI) and the response to subcutaneous alum-precipitated ovalbumin was followed in the draining lymph nodes.
199	23065152	Up-regulation of CXCR3 by GC B cells and AFCs and their migration toward its ligand CXCL10 are shown to depend on B cells' intrinsic T-bet, a transcription factor downstream of the IFN-γR signaling.
200	23071285	p27(Kip1) negatively regulates the magnitude and persistence of CD4 T cell memory.
201	23071285	Our studies ascribe a novel role for the cell cycle regulator p27(Kip1) as a prominent negative regulator of the establishment and long-term maintenance of Th1 CD4 T cell memory.
202	23071285	We demonstrate that p27(Kip1) might restrict the differentiation and survival of memory precursors by increasing the T-bet/Bcl-6 ratio in effector CD4 T cells.
203	23071285	By promoting apoptosis and contraction of effector CD4 T cells by mechanisms that are at least in part T cell intrinsic, p27(Kip1) markedly limits the abundance of memory CD4 T cells.
204	23071285	Furthermore, we causally link p27(Kip1)-dependent apoptosis to the decay of CD4 T cell memory, possibly by repressing the expression of γ-chain receptors and the downstream effector of the Wnt/β-catenin signaling pathway, Tcf-1.
205	23071285	We extend these findings by showing that the antagonistic effects of p27(Kip1) on CD4 T cell memory require its cyclin-dependent kinase-binding domain.
206	23071285	Collectively, these findings provide key insights into the mechanisms underlying the governance of peripheral CD4 T cell homeostasis and identify p27(Kip1) as a target to enhance vaccine-induced CD4 T cell memory.
207	23333555	We show that CD4+ and CD8+ Teffector/memory (T(EM)) and other subsets produce IL-17A following SEB stimulation.
208	23333555	We also show that IL-17A is co-produced with other pro-inflammatory cytokines (i.e., IL-2, IFN-γ and TNF-α).
209	23333555	Multifunctional IL-17A producing cells possess markers typical of the T(H)17/T(C)17 and T(H)1 subsets, including CCR6, IL-22, and transcription factors retinoic acid receptor-related orphan nuclear receptor (ROR)-γt and T-bet.
210	23338237	We observed the loss of the short-lived effector cell phenotype (reduced KLRG1(+), T-bet(hi), granzyme B(hi)), accompanied by an enhanced memory precursor phenotype at the effector (increased CD127(hi), IL-2(+)) and contraction phases (increased CD127(hi), IL-2(+), eomesodermin(hi)) of the CD8 response in the absence of RA signaling.
211	23359502	IL-2 produced by CD8+ immune T cells can augment their IFN-γ production independently from their proliferation in the secondary response to an intracellular pathogen.
212	23359502	In the current study, we examined the role of IL-2 in IFN-γ production by CD8(+) immune T cells in their secondary responses using T. gondii-specific CD8(+) T cell hybridomas and splenic CD8(+) immune T cells from chronically infected mice.
213	23359502	The majority (92%) of CD8(+) T cell hybridomas produced large amounts of IFN-γ only when a low amount (0.5 ng/ml) of exogenous IL-2 was provided in combination with T. gondii Ags.
214	23359502	Inhibition of cell proliferation by mitomycin C did not affect the enhancing effect of IL-2 on the IFN-γ production, and significant increases in transcription factor T-bet expression were associated with the IL-2-mediated IFN-γ amplification.
215	23359502	Splenic CD8(+) immune T cells produced similar low levels of IL-2 in the secondary response to T. gondii, and a blocking of IL-2 signaling by anti-IL-2Rα Ab or inhibitors of JAK1 and JAK3 significantly reduced IFN-γ production of the T cells.
216	23359502	This IL-2-mediated upregulation of IFN-γ production was observed in mitomycin C-treated CD8(+) immune T cells, thus independent from their cell division.
217	23359502	Therefore, endogenous IL-2 produced by CD8(+) immune T cells can play an important autocrine-enhancing role on their IFN-γ production in the secondary responses to T. gondii, suggesting an importance of induction of CD8(+) immune T cells with an appropriate IL-2 production for vaccine development.
218	23509806	CpG and interleukin-15 synergize to enhance IFN-γ production by activated CD8+ T cells.
219	23509806	Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8(+) T cells.
220	23509806	Paradoxically, we previously reported that IL-15 could enhance CD8(+) T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8(+) T cells.
221	23509806	The effect of CpG and IL-15 was also evident with CD8(+) T cells recovered from mice infected with the parasite Trypanosoma cruzi (T. cruzi) and restimulated with antigen.
222	23509806	The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8(+) T cells and CD4(+)CD25(+) regulatory T cells.
223	23509806	Although IFN-γ was not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8(+) T cells required expression of the IFN-γ-inducible transcription factor T-bet.
224	23911398	In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin.
225	24197893	Large numbers of SBR-CTA2/B-containing DC were found interacting with CD4(+) (T helper) cells, which costained for nuclear transcription factors T-bet or RORγt, identifying them as Th1 or Th17 cells.
226	24244265	Inhibition of CD4+CD25+ regulatory T cell function and conversion into Th1-like effectors by a Toll-like receptor-activated dendritic cell vaccine.
227	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.
228	24244265	The effect is therefore mediated by a soluble factor but was independent of both IL-6 and IL-12.
229	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.
230	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.
231	24244265	Inhibition of CD4+CD25+ regulatory T cell function and conversion into Th1-like effectors by a Toll-like receptor-activated dendritic cell vaccine.
232	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.
233	24244265	The effect is therefore mediated by a soluble factor but was independent of both IL-6 and IL-12.
234	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.
235	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.
236	24252697	In vitro, PS-F2 stimulated dendritic cells (DCs) to produce proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-12/IL-23 p40.
237	24252697	PS-F2 also stimulated DCs to express the maturation markers CD40, CD80, CD86, and MHC class II.
238	24252697	In a murine splenocyte culture, PS-F2 treatment resulted in elevated expression of T-bet and interferon (IFN)-γ in T lymphocytes.
239	24273578	HSP70/CD80 DNA vaccine inhibits airway remodeling by regulating the transcription factors T-bet and GATA-3 in a murine model of chronic asthma.
240	24296812	TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of T-box transcription factors T-bet with graded loss of Eomesodermin (Eomes) expression (T-bet(Hi)Eomes(Hi/Lo)) when compared with TNF-α(+) CD4(+) T cells expressing lower levels of both T-bet and Eomes (T-bet(-)Eomes(-)).
241	24296812	Furthermore, TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of perforin and interleukin (IL)-2 and displayed a terminally differentiated phenotype (CCR7(-)CD27(-)CD45RA(-)CD57(+)CD62L(-)).
242	24296812	In contrast, TNF-α(+) alone CMV-specific CD4(+) T cells were predominantly early-memory phenotype with a proportion of these cells displaying T memory stem-cell phenotype (CD95(+)CD45RA(+)CCR7(+)CD27(+)).
243	24296812	In vitro stimulation of CMV-specific CD4(+) T cells with viral antigen in the presence of IL-12 was sufficient to dramatically change the transcriptional and functional profile of TNF-α(+) CD4(+) T cells, whereas TNF-α(+) and IFN-γ(+) CD4(+) T cells remained unaltered.
244	24363764	The aim of this study is to determine whether the regulatory role of T cell vaccination (TCV) is through inhibition of Th1/Th17/Tfh and production of autoantibodies on collagen-induced arthritis (CIA).
245	24363764	In addition, inhibition of Th1/Th17/Tfh frequencies led to the reduced expression of T-bet, ROR α , ROR γ t, and Bcl6.
246	24421047	Upregulation of the transcription factor T-bet is correlated with the strength of protection against secondary challenge with the live vaccine strain (LVS) of Francisella tularensis.
247	24421047	Lungs of LVS-infected T-bet-KO mice contained fewer lymphocytes and more neutrophils and interleukin-17 than WT mice.
248	24421047	LVS-vaccinated WT or KO mice controlled intracellular bacterial replication in an in vitro coculture system, but cultures with T-bet-KO splenocyte supernatants contained less IFN-γ and increased amounts of tumor necrosis factor alpha.
249	24421047	Upregulation of the transcription factor T-bet is correlated with the strength of protection against secondary challenge with the live vaccine strain (LVS) of Francisella tularensis.
250	24421047	Lungs of LVS-infected T-bet-KO mice contained fewer lymphocytes and more neutrophils and interleukin-17 than WT mice.
251	24421047	LVS-vaccinated WT or KO mice controlled intracellular bacterial replication in an in vitro coculture system, but cultures with T-bet-KO splenocyte supernatants contained less IFN-γ and increased amounts of tumor necrosis factor alpha.
252	24421047	Upregulation of the transcription factor T-bet is correlated with the strength of protection against secondary challenge with the live vaccine strain (LVS) of Francisella tularensis.
253	24421047	Lungs of LVS-infected T-bet-KO mice contained fewer lymphocytes and more neutrophils and interleukin-17 than WT mice.
254	24421047	LVS-vaccinated WT or KO mice controlled intracellular bacterial replication in an in vitro coculture system, but cultures with T-bet-KO splenocyte supernatants contained less IFN-γ and increased amounts of tumor necrosis factor alpha.
255	24497611	Recently, we reported that the combination of CpG and IL-21 (CpG/IL-21) can induce granzyme B (GrB)-dependent apoptosis in B-CLL cells.
256	24497611	APC- and CTL-typical molecules found to be up-regulated in CpG/IL-21-stimulated B-CLL cells include GrB, perforin, T-bet, monokine-induced by IFN-γ and IFN-γ-inducible protein 10 (IP-10), as well as molecules important for cell adhesion, antigen cross-presentation and costimulation.
257	24497611	Also induced are molecules involved in GrB induction, trafficking and processing, whereas the GrB inhibitor Serpin B9 [formerly proteinase inhibitor-9 (PI-9)] is down-modulated by CpG/IL-21.
258	24568548	Specific TEM cells differentiated into cells with a KLRG1(High) CD27(Low) CD43(Low) CD183(Low)T-bet(High) Eomes(Low) phenotype and capable to produce simultaneously the antiparasitic mediators IFNγ and TNF.
259	24579458	We found that this peptide induced the expression of T-bet and TATA box binding protein-associated factor that can induce the chromatin remodeling of ifn-gamma gene, and as a result induced Th1 differentiation even in the absence of IFN-gamma and IL-12.
260	24579458	Next, we established an in vitro CTL differentiation system using Peptide-25, Peptide-25 specific CD4+ T cells, OVA specific CD8+ T cells and splenic DC.
261	24579458	By using this system, we found that CD4+ T cells activated DC even in the absence of IFN-gamma and CD40 ligand association, and the activated DC induced the functional differentiation of CTL.
262	24717539	Such NA-mediated costimulation crucially induces Th2 differentiation by suppressing T-bet expression, followed by the induction of GATA-3 and Th2 cytokines.
263	24778441	Longitudinal requirement for CD4+ T cell help for adenovirus vector-elicited CD8+ T cell responses.
264	24778441	Our data demonstrate that induction and maintenance of CD8(+) T cell responses by Ad vector immunization is longitudinally dependent on CD4(+) T cell help for a prolonged period.
265	24778441	Depletion of CD4(+) T cells in wild type mice within the first 8 d following Ad immunization resulted in dramatically reduced induction of Ag-specific CD8(+) T cells, decreased T-bet and eomesodermin expression, impaired KLRG1(+) effector differentiation, and atypical expression of the memory markers CD127, CD27, and CD62L.
266	24778441	Depletion of CD4(+) T cells between weeks 1 and 4 following immunization resulted in increased contraction of memory CD8(+) T cells.
267	24778441	These data demonstrate a prolonged temporal requirement for CD4(+) T cell help for vaccine-elicited CD8(+) T cell responses in mice.
268	24778441	These findings have important implications in the design of vaccines aimed at eliciting CD8(+) T cell responses and may provide insight into the impaired immunogenicity of vaccines in the context of AIDS and other CD4(+) T cell immune deficiencies.
269	24837104	Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1.
270	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.
271	24860792	TGF-β, IL-10, and FoxP3 were not up-regulated, indicating no activation of regulatory T cells.
272	24898389	Rapamycin enhanced IL-12 signaling by upregulating IL-12 receptor β2 expression and signal transducer and activator of transcription factor 4 phosphorylation in CTLs during early infection.
273	24898389	In addition, rapamycin continually suppressed T-bet expression in both wild-type and IL-12 receptor knockout CTLs.
274	24905579	A better understanding of the role of CD4+ and CD8+ T cells, which are both important to TB protection, is essential to unravel the mechanisms of protection and to identify the key antigens seen by these T cells.
275	24905579	An Rv2034-specific CD4+ T-cell clone expressed the Th1 markers T-bet, IFN-γ, TNF-α, IL-2 and the cytotoxicity related markers granzyme B and CD107a as measured by flow cytometry.
276	24943726	We pursue in-depth analysis of the endogenous mycobacteria-specific CD4(+) T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites for superior protection against tuberculosis. rBCG induced higher numbers and proportions of antigen-specific memory CD4(+) T cells than BCG, with a CXCR5(+)CCR7(+) phenotype and low expression of the effector transcription factors T-bet and Bcl-6.
277	25047384	Here, we used Tbx21(-/-) mice deficient for T-bet, a regulator of Th1 CD4(+) T-cell differentiation, to examine the effect of Th1 CD4(+) T cells on the immune protection to nonlethal murine malaria Plasmodium yoelii 17XNL.
278	25047384	However, Tbx21(-/-) mice produced greater numbers of Foxp3(+) CD25(+) regulatory CD4(+) T cells, which may contribute to the early contraction of T cells.
279	25424811	We found at the mucosal site an inhibition of the gene expression corresponding to IL-13 and Gata-3, with an induction of IFN-γ and T-bet.
280	25473946	In contrast to the ability of long-lived CD8(+) memory T cells to mediate protection against systemic viral infections, the relationship between CD4(+) T cell memory and acquired resistance against infectious pathogens remains poorly defined.
281	25473946	We found that pre-existing, CD44(+)CD62L(-)T-bet(+)Ly6C+ effector (T(EFF)) cells that are short-lived in the absence of infection and are not derived from memory cells reactivated by secondary challenge, mediate concomitant immunity.
282	25473946	Upon adoptive transfer and challenge, non-dividing Ly6C(+) T(EFF) cells preferentially homed to the skin, released IFN-γ, and conferred protection as compared to CD44(+)CD62L(-)Ly6C(-) effector memory or CD44(+)CD62L(+)Ly6C(-) central memory cells.
283	25505279	Chronic lymphocytic leukemia cells express CD38 in response to Th1 cell-derived IFN-γ by a T-bet-dependent mechanism.
284	25505279	The expression of the transcription factor T-bet in peripheral blood CLL cells significantly correlated with CD38 expression, and transient transfection of CLL cells with T-bet resulted in T-bet(hi)CD38(hi) cells.
285	25505279	Finally, chromatin immunoprecipitation experiments revealed that T-bet can bind to regulatory regions of the CD38 gene.
286	25505279	These data suggest that CLL cells attract CLL-specific Th cells and initiate a positive feedback loop with upregulation of T-bet, CD38, and type 1 chemokines allowing further recruitment of Th cells and increased type 1 cytokine secretion.
287	25505279	This insight provides a cellular and molecular mechanism that links the inflammatory signature observed in CLL pathogenesis with CD38 expression and aggressive disease and suggests that targeting the IFN-γ/IFN-γR/JAK/STAT/T-bet/CD38 pathway could play a role in the therapy of CLL.
288	25505279	Chronic lymphocytic leukemia cells express CD38 in response to Th1 cell-derived IFN-γ by a T-bet-dependent mechanism.
289	25505279	The expression of the transcription factor T-bet in peripheral blood CLL cells significantly correlated with CD38 expression, and transient transfection of CLL cells with T-bet resulted in T-bet(hi)CD38(hi) cells.
290	25505279	Finally, chromatin immunoprecipitation experiments revealed that T-bet can bind to regulatory regions of the CD38 gene.
291	25505279	These data suggest that CLL cells attract CLL-specific Th cells and initiate a positive feedback loop with upregulation of T-bet, CD38, and type 1 chemokines allowing further recruitment of Th cells and increased type 1 cytokine secretion.
292	25505279	This insight provides a cellular and molecular mechanism that links the inflammatory signature observed in CLL pathogenesis with CD38 expression and aggressive disease and suggests that targeting the IFN-γ/IFN-γR/JAK/STAT/T-bet/CD38 pathway could play a role in the therapy of CLL.
293	25505279	Chronic lymphocytic leukemia cells express CD38 in response to Th1 cell-derived IFN-γ by a T-bet-dependent mechanism.
294	25505279	The expression of the transcription factor T-bet in peripheral blood CLL cells significantly correlated with CD38 expression, and transient transfection of CLL cells with T-bet resulted in T-bet(hi)CD38(hi) cells.
295	25505279	Finally, chromatin immunoprecipitation experiments revealed that T-bet can bind to regulatory regions of the CD38 gene.
296	25505279	These data suggest that CLL cells attract CLL-specific Th cells and initiate a positive feedback loop with upregulation of T-bet, CD38, and type 1 chemokines allowing further recruitment of Th cells and increased type 1 cytokine secretion.
297	25505279	This insight provides a cellular and molecular mechanism that links the inflammatory signature observed in CLL pathogenesis with CD38 expression and aggressive disease and suggests that targeting the IFN-γ/IFN-γR/JAK/STAT/T-bet/CD38 pathway could play a role in the therapy of CLL.
298	25505279	Chronic lymphocytic leukemia cells express CD38 in response to Th1 cell-derived IFN-γ by a T-bet-dependent mechanism.
299	25505279	The expression of the transcription factor T-bet in peripheral blood CLL cells significantly correlated with CD38 expression, and transient transfection of CLL cells with T-bet resulted in T-bet(hi)CD38(hi) cells.
300	25505279	Finally, chromatin immunoprecipitation experiments revealed that T-bet can bind to regulatory regions of the CD38 gene.
301	25505279	These data suggest that CLL cells attract CLL-specific Th cells and initiate a positive feedback loop with upregulation of T-bet, CD38, and type 1 chemokines allowing further recruitment of Th cells and increased type 1 cytokine secretion.
302	25505279	This insight provides a cellular and molecular mechanism that links the inflammatory signature observed in CLL pathogenesis with CD38 expression and aggressive disease and suggests that targeting the IFN-γ/IFN-γR/JAK/STAT/T-bet/CD38 pathway could play a role in the therapy of CLL.
303	25505279	Chronic lymphocytic leukemia cells express CD38 in response to Th1 cell-derived IFN-γ by a T-bet-dependent mechanism.
304	25505279	The expression of the transcription factor T-bet in peripheral blood CLL cells significantly correlated with CD38 expression, and transient transfection of CLL cells with T-bet resulted in T-bet(hi)CD38(hi) cells.
305	25505279	Finally, chromatin immunoprecipitation experiments revealed that T-bet can bind to regulatory regions of the CD38 gene.
306	25505279	These data suggest that CLL cells attract CLL-specific Th cells and initiate a positive feedback loop with upregulation of T-bet, CD38, and type 1 chemokines allowing further recruitment of Th cells and increased type 1 cytokine secretion.
307	25505279	This insight provides a cellular and molecular mechanism that links the inflammatory signature observed in CLL pathogenesis with CD38 expression and aggressive disease and suggests that targeting the IFN-γ/IFN-γR/JAK/STAT/T-bet/CD38 pathway could play a role in the therapy of CLL.
308	25687199	TBG also dramatically enhanced splenocyte proliferative responses to concanavalin A, lipopolysaccharide, and OVA and substantially increased T-bet mRNA levels and the CD3(+)/CD3(+)CD4(+)/CD3(+)CD8(+) phenotype in splenocytes from OVA-immunized mice.
309	25768938	Transcription factor expression patterns in SIV-specific CD8+ T cells in SIVΔnef-vaccinated animals were distinct from those observed in purified CD8+ T cell subsets obtained from naïve animals, and were intermediate to expression profiles of purified central memory and effector memory T cells.
310	25768938	Expression of transcription factors associated with effector differentiation, such as ID2 and RUNX3, were decreased over time, while expression of transcription factors associated with quiescence or memory differentiation, such as TCF7, BCOR and EOMES, increased.
311	25768938	CD8+ T cells specific for a more conserved epitope expressed higher levels of TBX21 and BATF, and appeared more effector-like than cells specific for an escaped epitope, consistent with continued activation by replicating vaccine virus.
312	25907170	RpfE induces DC maturation by increasing expression of surface molecules and the production of IL-6, IL-1β, IL-23p19, IL-12p70, and TNF-α but not IL-10.
313	25907170	This induction is mediated through TLR4 binding and subsequent activation of ERK, p38 MAPKs, and NF-κB signaling.
314	25907170	RpfE-treated DCs effectively caused naïve CD4(+) T cells to secrete IFN-γ, IL-2, and IL-17A, which resulted in reciprocal expansions of the Th1 and Th17 cell response along with activation of T-bet and RORγt but not GATA-3.
315	25959574	After challenge with E. tarda, live cell (LC)-vaccinated fish showed high survival rates, high IFN-g and T-bet gene expression levels, and increased cytotoxic T lymphocytes (CTLs).
316	25959574	In addition, FKC vaccination induced high IL-4/13A and IL-10 expression levels and increased antibody titers, whereas Th1-like responses were suppressed.
317	26026061	Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4(+)T-bet(+) T cells and CD8(+)SIINFEKEL(+) T cells.
318	26093207	Furthermore, significant induction of TLR9, Mx and IL-1β was observed in the spleen on day 7 post-vaccination, supporting that the vaccine could trigger TLR9 signaling.
319	26093207	Interestingly, at week 2 the ODN appeared to induce a Th1-like response, as indicated by upregulation of T-bet (a Th1 marker) and downregulation of GATA-3 (a Th2 marker).
320	26220166	CD161(int)CD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut.
321	26220166	Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including antiviral populations that display a memory phenotype.
322	26220166	These memory CD161(int)CD8+ T cells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence.
323	26220166	Furthermore, this population was characterized by enhanced polyfunctionality, increased levels of cytotoxic mediators, and high expression of the transcription factors T-bet and eomesodermin (EOMES).
324	26220166	Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T-cell populations in humans.
325	26297758	Vaccination Produces CD4 T Cells with a Novel CD154-CD40-Dependent Cytolytic Mechanism.
326	26297758	We demonstrate that immunization with a recombinant protein Ag and GLA-SE also induces granzyme A expression in CD4 T cells and produces cytolytic cells that can be detected in vivo.
327	26297758	Surprisingly, these in vivo CTLs were CD4 T cells, not CD8 T cells, and this cytolytic activity was not dependent on granzyme A/B or perforin.
328	26297758	Unlike previously reported CD4 CTLs, the transcription factors Tbet and Eomes were not necessary for their development.
329	26297758	CTL activity was also independent of the Fas ligand-Fas, TRAIL-DR5, and canonical death pathways, indicating a novel mechanism of CTL activity.
330	26297758	Rather, the in vivo CD4 CTL activity induced by vaccination required T cell expression of CD154 (CD40L) and target cell expression of CD40.
331	26297758	Thus, vaccination with a TLR4 agonist adjuvant induces CD4 CTLs, which kill through a previously unknown CD154-dependent mechanism.
332	26344618	Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity.
333	26036767	After coimmunization of mice with sFliC and STm there was a reduction in Th1 T cells (T-bet(+) IFN-γ(+) CD4 T cells) compared to STm alone and there was impaired clearance of STm.