Caramalho, I.Lopes-Carvalho, T.Ostler, D.Zelenay, S.Haury, MDemengeot, J2010-08-112010-08-112003-02-17Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. (2003). “Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide”. Journal of Experimental Medicine. 197 (4): 403-411http://hdl.handle.net/10400.7/161Regulatory CD4 T cells (Treg) control inflammatory reactions to commensal bacteria and opportunist pathogens. Activation of Treg functions during these processes might be mediated by host-derived proinflammatory molecules or directly by bacterial products. We tested the hypothesis that engagement of germline-encoded receptors expressed by Treg participate in the triggering of their function. We report that the subset of CD4 cells known to exert regulatory functions in vivo (CD45RB(low) CD25(+)) selectively express Toll-like receptors (TLR)-4, -5, -7, and -8. Exposure of CD4(+) CD25(+) cells to the TLR-4 ligand lipopolysaccharide (LPS) induces up-regulation of several activation markers and enhances their survival/proliferation. This proliferative response does not require antigen-presenting cells and is augmented by T cell receptor triggering and interleukin 2 stimulation. Most importantly, LPS treatment increases CD4(+) CD25(+) cell suppressor efficiency by 10-fold and reveals suppressive activity in the CD4(+) CD45RB(low) CD25(-) subset that when tested ex-vivo, scores negative. Moreover, LPS-activated Treg efficiently control naive CD4 T cell-dependent wasting disease. These findings provide the first evidence that Treg respond directly to proinflammatory bacterial products, a mechanism that likely contributes to the control of inflammatory responsesengInflammationToleranceLymphocytesRegulationInnate immunityjournal article