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Distinct Effects of T-bet in TH1 Lineage Commitment and IFN- Production in CD4 and CD8 T Cells
Susanne J. Szabo,1Brandon M. Sullivan,1Claudia Stemmann,1Abhay R. Satoskar,3Barry P. Sleckman,4Laurie H. Glimcher12*
T-bet is a member of the T-box family of transcription
factors that appears to regulate lineage commitment in CD4 T helper(TH) lymphocytes in part by activating the hallmark
TH1 cytokine,interferon- (IFN-). IFN- is also
produced by natural killer(NK) cells and most prominently by CD8
cytotoxic T cells, andis vital for the control of microbial pathogens.
Although T-betis expressed in all these cell types, it is required for
controlof IFN- production in CD4 and NK cells, but not in CD8
cells.This difference is also apparent in the function of these cellsubsets. Thus, the regulation of a single cytokine, IFN-, iscontrolled by distinct transcriptional mechanisms within the Tcell
lineage.
1 Department of Immunology and Infectious
Diseases, Harvard School of Public Health and
2 Department of Medicine, Harvard Medical School,
Boston, MA 02115, USA.
3 Department of Microbiology,
Ohio State University, Columbus, OH 43210, USA.
4 Department of Pathology and Immunology, Washington
University School of Medicine, St. Louis, MO 63110, USA.
*
To whom correspondence should be addressed. E-mail:
lglimche{at}hsph.harvard.edu
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T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
T. Usui, J. C. Preiss, Y. Kanno, Z. J. Yao, J. H. Bream, J. J. O'Shea, and W. Strober (2006)
J. Exp. Med.
203, 755-766
|Abstract »|Full Text »|PDF »
IL-27 Suppresses CD28-Medicated IL-2 Production through Suppressor of Cytokine Signaling 3..
T. Owaki, M. Asakawa, S. Kamiya, K. Takeda, F. Fukai, J. Mizuguchi, and T. Yoshimoto (2006)
J. Immunol.
176, 2773-2780
|Abstract »|Full Text »|PDF »
Nuclear Receptors and Autoimmune Disease: The Potential of PPAR Agonists to Treat Multiple Sclerosis.
M. K. Racke, A. R. Gocke, M. Muir, A. Diab, P. D. Drew, and A. E. Lovett-Racke (2006)
J. Nutr.
136, 700-703
|Abstract »|Full Text »|PDF »
Responsiveness of Naive CD4 T Cells to Polarizing Cytokine Determines the Ratio of Th1 and Th2 Cell Differentiation.
N. Mikhalkevich, B. Becknell, M. A. Caligiuri, M. D. Bates, R. Harvey, and W.-p. Zheng (2006)
J. Immunol.
176, 1553-1560
|Abstract »|Full Text »|PDF »
Tec Kinases Itk and Rlk Are Required for CD8+ T Cell Responses to Virus Infection Independent of Their Role in CD4+ T Cell Help.
L. O. Atherly, M. A. Brehm, R. M. Welsh, and L. J. Berg (2006)
J. Immunol.
176, 1571-1581
|Abstract »|Full Text »|PDF »
T-bet Down-Modulation in Tolerized Th1 Effector CD4 Cells Confers a TCR-Distal Signaling Defect That Selectively Impairs IFN-{gamma} Expression.
M. Long, A. M. Slaiby, A. T. Hagymasi, M. A. Mihalyo, A. C. Lichtler, S. L. Reiner, and A. J. Adler (2006)
J. Immunol.
176, 1036-1045
|Abstract »|Full Text »|PDF »
T-helper cell type-2 regulation in allergic disease.
S. N. Georas, J. Guo, U. De Fanis, and V. Casolaro (2005)
Eur. Respir. J.
26, 1119-1137
|Abstract »|Full Text »|PDF »
Stat1-Dependent Synergistic Activation of T-bet for IgG2a Production during Early Stage of B Cell Activation.
A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells.
G. H. Underhill, D. G. Zisoulis, K. P. Kolli, L. G. Ellies, J. D. Marth, and G. S. Kansas (2005)
Blood
106, 3867-3873
|Abstract »|Full Text »|PDF »
T-bet is required for optimal proinflammatory CD4+ T-cell trafficking.
G. M. Lord, R. M. Rao, H. Choe, B. M. Sullivan, A. H. Lichtman, F. W. Luscinskas, and L. H. Glimcher (2005)
Blood
106, 3432-3439
|Abstract »|Full Text »|PDF »
IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508.
E. S. Hwang, J.-H. Hong, and L. H. Glimcher (2005)
J. Exp. Med.
202, 1289-1300
|Abstract »|Full Text »|PDF »
Production in CD4 and CD8 T Cells
(IFN-
