Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide.
Regulatory 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 responses.
Caramalho
Iris
I
Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal.
Lopes-Carvalho
Thiago
T
Ostler
Dominique
D
Zelenay
Santiago
S
Haury
Matthias
M
Demengeot
Jocelyne
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D029721:Drosophila Proteins; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D019282:Wasting Syndrome / Q000209:etiology
D029721:Drosophila Proteins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D017493:Leukocyte Common Antigens