A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis

Hervé Groux, Anne O'Garra, Mike Bigler, Matthieu Rouleau, Svetlana Antonenko, Jan E. De Vries, Maria Grazia Roncarolo

Research output: Contribution to journalArticlepeer-review

Abstract

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 active 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+CD45RB(high) 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 languageEnglish
Pages (from-to)737-742
Number of pages6
JournalNature
Volume389
Issue number6652
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • General

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