297 BACTERIAL FLAGELLIN ACTS AS A COSTIMULATORY SIGNAL FOR HUMAN T CELL RECEPTOR ACTIVATION

Abstract

<h3></h3> Toll-like receptors (TLRs) are pattern recognition molecules expressed by cells of the innate immune system that mediate inflammatory responses by recognizing microbial patterns, including lipopolysaccharide and bacterial flagellin. TLRs are thought to influence adaptive immunity indirectly by enhancing antigen presentation; however, pattern recognition molecules are also expressed on cells of the adaptive immune system. Therefore, to investigate the ability of TLR ligands to directly induce adaptive immune responses, we evaluated the expression and function of TLRs on human T cells. We found that human peripheral blood T cells and T cell clones express TLRs and exposure of T cells to TLR ligands enhanced their response to T cell receptor activation. Bacterial flagellin, a microbial pattern commonly used for motility by enteric pathogens and a TLR5 ligand, was a potent inducer of primary human T cells and T cell clones. To investigate the mechanism whereby T cells respond to TLR ligation, we used an immortalized human T cell line, Jurkat. We found that flagellin activates a signaling pathway in T cells involving p38 mitogen-activated protein (MAP) kinase, and that in combination with TCR activation, p38 MAP kinase is activated to a greater extent. The potentiating effect of bacterial flagellin for TCR-activation also resulted in the production of IL-2 from Jurkat cells, indicating that TLR ligands act as a costimulatory signal for T cells. Our data suggest that microbial pattern molecules may directly activate the adaptive immune response by acting as an adjuvant for antigen-specific T cells. The presence of bacterial flagellin on bacteria in the intestine may potentiate inflammation by directly activating T cells.