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Publication : Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection.

First Author  Ravindran R Year  2005
Journal  J Immunol Volume  175
Issue  7 Pages  4603-10
PubMed ID  16177105 Mgi Jnum  J:118948
Mgi Id  MGI:3700859 Doi  10.4049/jimmunol.175.7.4603
Citation  Ravindran R, et al. (2005) Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. J Immunol 175(7):4603-10
abstractText  Despite the recognized role of the T-bet transcription factor in the differentiation of Th1 cells, T-bet-deficient mice can develop small numbers of IFN-gamma-producing CD4 T cells. Although these are not sufficient to allow normal handling of some pathogens, T-bet-deficient mice do resolve infection with the intracellular pathogen Listeria monocytogenes. In contrast, we report that expression of T-bet is required for resistance to Salmonella infection. T-bet-deficient mice succumbed to infection with attenuated Salmonella and did not generate IFN-gamma-producing CD4 T cells or isotype-switched Salmonella-specific Ab responses. Spleen cells from Salmonella-infected T-bet-deficient mice secreted increased levels of IL-10, but not IL-4, upon in vitro restimulation. A Salmonella-specific TCR transgenic adoptive transfer system was used to further define the involvement of T-bet expression in the development of Salmonella-specific Th1 cells. Wild-type Salmonella-specific CD4 T cells activated in T-bet-deficient recipient mice displayed no defect in clonal expansion, contraction, or IFN-gamma production. In contrast, T-bet-deficient, Salmonella-specific CD4 T cells activated in wild-type recipient mice produced less IFN-gamma and more IL-2 upon in vivo restimulation. Therefore, expression of T-bet by CD4 T cells is required for the development of Salmonella-specific Th1 cells, regulation of IL-10 production, and resistance to Salmonella infection.
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