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Expression of T-bet by CD4 T Cells Is Essential for Resistance to Salmonella Infection¹

Rajesh Ravindran^*, Joseph Foley^*, Thomas Stoklasek^*, Laurie H. Glimcher and Stephen J. McSorley^2,*

^* Department of Medicine, Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and Department of Immunology and Infectious Diseases, Harvard School of Public Health, and Department of Medicine, Harvard Medical School, Boston, MA 02115

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--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--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- production. In contrast, T-bet-deficient, Salmonella-specific CD4 T cells activated in wild-type recipient mice produced less IFN- 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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The JI 2005 175: 4159-4160. [Full Text]  

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