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Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115
T cell-mediated adaptive immunity is required to help clear infection with the facultative intracellular bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), yet development of T cell-mediated adaptive immunity to S. Typhimurium has been described as slow and inefficient. A key step in inducing T cell-mediated adaptive immunity is T cell priming; the activation, proliferation, and differentiation of naive T cells following initial encounter with Ag. We previously demonstrated that S. Typhimurium had a direct inhibitory effect on naive T cells from mouse, blocking their proliferation. In this study, we show that S. Typhimurium down-modulates expression of the TCR β-chain, a molecule that is essential for Ag recognition and T cell function. Specifically, we demonstrate that reduced amounts of surface and intracellular TCR-β protein and decreased levels of tcrβ transcript are expressed by T cells cultured in the presence of S. Typhimurium. We further show that the down-modulation of TCR-β expression requires contact between S. Typhimurium and the T cells and that once contact occurs, a factor capable of reducing TCR-β expression is secreted. These results provide new insight into the mechanism by which S. Typhimurium may inhibit T cell priming and avoid clearance by the adaptive immune system.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Grant AI055962 from the National Institutes of Health (to M.N.S.). A.W.M.v.d.V. was supported in part by Grant P30 DK34845 from the Harvard Digestive Diseases Center, National Institutes of Health.
2 Current address: Department of Molecular Genetics and Microbiology, and Center for Infectious Diseases, 130 Life Sciences Building, State University of New York, Stony Brook, NY 11794.
3 Address correspondence and reprint requests to Dr. Michael N. Starnbach, Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115. E-mail address: starnbach{at}hms.harvard.edu
4 Abbreviations used in this paper: S. Typhimurium, Salmonella enterica serovar Typhimurium; TTSS, type three secretion system; SPI, Salmonella pathogenicity island.
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