Down-Modulation of TCR Expression by Salmonella enterica serovar Typhimurium
Journal of Immunology
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
... 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 ␤-chain, a molecule that is essential for Ag recognition and T cell function. Specifically, we demonstrate that reduced amounts of surface and intracellular TCR-␤ protein and decreased levels of tcr␤ transcript are expressed by T cells cultured in the presence of S. Typhimurium. We further show that the down-modulation of TCR-␤ expression requires contact between S. Typhimurium and the T cells and that once contact occurs, a factor capable of reducing TCR-␤ 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. Bacteria were grown under aerobic conditions at 37°C in 3 ml of Luria-Bertani broth (Difco). Heat-killed bacteria were obtained by incubating bacterial suspensions at 65°C for 20 min. Escherichia coli DH5␣, wild-type S. Typhimurium (14028; American Type Culture Collection), an isogenic virulence plasmid-cured (a derivative of American Type Culture Collection 14028), and a set of isogenic invA, spiB, phoP, and constitutively expressing phoP mutant strains were published previously (25). S. Typhimurium-deficient for sti were provided by J. Mekalanos (Harvard 4 Abbreviations used in this paper: S. Typhimurium, Salmonella enterica serovar Typhimurium; TTSS, type three secretion system; SPI, Salmonella pathogenicity island.