Down-modulation of TCR expression by Salmonella enterica serovar Typhimurium.
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 beta-chain, a molecule that is essential for Ag recognition and T cell function. Specifically, we demonstrate that reduced amounts of surface and intracellular TCR-beta protein and decreased levels of tcrbeta transcript are expressed by T cells cultured in the presence of S. Typhimurium. We further show that the down-modulation of TCR-beta expression requires contact between S. Typhimurium and the T cells and that once contact occurs, a factor capable of reducing TCR-beta 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.
van der Velden
Adrianus W M
AW
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Dougherty
Jeffrey T
JT
Starnbach
Michael N
MN
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014774:Virulence
D001426:Bacterial Proteins; D007155:Immunologic Factors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; D009569:Nitric Oxide; D015232:Dinoprostone