Cutting edge: Lipopolysaccharide induces IL-10-producing regulatory CD4+ T cells that suppress the CD8+ T cell response.
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.
den Haan
Joke M M
JM
Molecular Cell Biology and Immunology, Free University Medical Center, 1007 MB Amsterdam, The Netherlands. j.denhaan@vumc.nl
Kraal
Georg
G
Bevan
Michael J
MJ
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*
D015704:CD4 Antigens; D008024:Ligands; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D016753:Interleukin-10