Interleukin 10 is a growth factor for a population of regulatory T cells.
Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such suppression. Here, we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RBhigh splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.
Asseman
C
C
Nuffield Dept of Surgery, University of Oxford, John Radcliffe Hospital, UK.
Powrie
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F
D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002999:Clone Cells / Q000502:physiology; D003092:Colitis / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID
D000941:Antigens; D007376:Interleukin-2; D016753:Interleukin-10; D017493:Leukocyte Common Antigens