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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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A. M. Intlekofer, A. Banerjee, N. Takemoto, S. M. Gordon, C. S. DeJong, H. Shin, C. A. Hunter, E. J. Wherry, T. Lindsten, and S. L. Reiner (2008)
Science
321, 408-411
|Abstract »|Full Text »|PDF »
T-Bet Plays a Key Role in NK-Mediated Control of Melanoma Metastatic Disease.
M. B. F. Werneck, G. Lugo-Villarino, E. S. Hwang, H. Cantor, and L. H. Glimcher (2008)
J. Immunol.
180, 8004-8010
|Abstract »|Full Text »|PDF »
Overlapping and Distinct Roles of STAT4 and T-bet in the Regulation of T Cell Differentiation and Allergic Airway Inflammation.
S. Furuta, S.-i. Kagami, T. Tamachi, K. Ikeda, M. Fujiwara, A. Suto, K. Hirose, N. Watanabe, Y. Saito, I. Iwamoto, et al. (2008)
J. Immunol.
180, 6656-6662
|Abstract »|Full Text »|PDF »
Functional Th1 Cells Are Required for Surgical Adhesion Formation in a Murine Model.
A. O. Tzianabos, M. A. Holsti, X.-X. Zheng, A. F. Stucchi, V. K. Kuchroo, T. B. Strom, L. H. Glimcher, and W. W. Cruikshank (2008)
J. Immunol.
180, 6970-6976
|Abstract »|Full Text »|PDF »
Unconventional Association of the Polycomb Group Proteins with Cytokine Genes in Differentiated T Helper Cells.
E. Jacob, R. Hod-Dvorai, S. Schif-Zuck, and O. Avni (2008)
J. Biol. Chem.
283, 13471-13481
|Abstract »|Full Text »|PDF »
Immunological and Genetic Evidence for a Crucial Role of IL-10 in Cutaneous Lesions in Humans Infected with Leishmania braziliensis.
A. Salhi, V. Rodrigues Jr., F. Santoro, H. Dessein, A. Romano, L. R. Castellano, M. Sertorio, S. Rafati, C. Chevillard, A. Prata, et al. (2008)
J. Immunol.
180, 6139-6148
|Abstract »|Full Text »|PDF »
Blockade of transforming growth factor {beta} upregulates T-box transcription factor T-bet, and increases T helper cell type 1 cytokine and matrix metalloproteinase-3 production in the human gut mucosa.
A. Di Sabatino, K. M. Pickard, D. Rampton, L. Kruidenier, L. Rovedatti, N. A. B. Leakey, G. R. Corazza, G. Monteleone, and T. T. MacDonald (2008)
Gut
57, 605-612
|Abstract »|Full Text »|PDF »
Production in CD4 and CD8 T Cells
(IFN-
