title: Cutting edge: Lipopolysaccharide induces IL-10-producing regulatory CD4+ T cells that suppress the CD8+ T cell response.
abstract: TLR ligands are potent activators of dendritic cells and therefore function as adjuvants for the induction of immune responses. We analyzed the capacity of TLR ligands to enhance CD8+ T cell responses toward soluble protein Ag. Immunization with OVA together with LPS or poly(I:C) elicited weak CD8+ T cell responses in wild-type C57BL/6 mice. Surprisingly, these responses were greatly increased in mice lacking CD4+ T cells indicating the induction of regulatory CD4+ T cells. In vivo, neutralization of IL-10 completely restored CD8+ T cell responses in wild-type mice and OVA-specific IL-10 producing CD4+ T cells were detected after immunization with OVA plus LPS. Our study shows that TLR ligands not only activate the immune system but simultaneously induce Ag specific, IL-10-producing regulatory Tr1 cells that strongly suppress CD8+ T cell responses. In this way, excessive activation of the immune system may be prevented.
authors: Molecular Cell Biology and Immunology, Free University Medical Center, 1007 MB Amsterdam, The Netherlands. j.denhaan@vumc.nl
authors: Joke M M
authors: JM
authors: den Haan
authors: Georg
authors: G
authors: Kraal
authors: Michael J
authors: MJ
authors: Bevan
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D008024:Ligands; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D016753:Interleukin-10