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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.

Original publication

DOI

10.1136/gut.42.2.157

Type

Journal article

Journal

Gut

Publication Date

02/1998

Volume

42

Pages

157 - 158

Addresses

Nuffield Dept of Surgery, University of Oxford, John Radcliffe Hospital, UK.

Keywords

Lymphocyte Subsets, CD4-Positive T-Lymphocytes, Clone Cells, Animals, Humans, Mice, Mice, SCID, Colitis, Antigens, CD45, Interleukin-2, Interleukin-10, Antigens, Lymphocyte Activation, Cell Division, Immune Tolerance