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

Rajesh Ravindran, Joseph Foley, Thomas Stoldasek, Laurie H. Glimcher, Stephen J Mcsorley

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107 Scopus citations

Abstract

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-γ-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-γ-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, bet not DL-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-deflcient recipient mice displayed no defect in clonal expansion, contraction, or IFN-γ production. In contrast, T-bet-deficient, Salmonella-specific CD4 T cells activated in wild-type recipient mice produced less IFN-γ and more EL-2 upon in vivo restimulation. Therefore, expression of T-bet by CD4 T cells is required for the development of Salmonella-specific Till cells, regulation of IL-10 production, and resistance to Salmonella infection.

Original languageEnglish (US)
Pages (from-to)4603-4610
Number of pages8
JournalJournal of Immunology
Volume175
Issue number7
StatePublished - Oct 1 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Ravindran, R., Foley, J., Stoldasek, T., Glimcher, L. H., & Mcsorley, S. J. (2005). Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. Journal of Immunology, 175(7), 4603-4610.