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

✍ Scribed by Roncarolo, Maria Grazia; Groux, Hervé; O'Garra, Anne; Bigler, Mike; Rouleau, Matthieu; Antonenko, Svetlana; de Vries, Jan E.

• Book ID: 109800060
• Publisher: Nature Publishing Group
• Year: 1997
• Tongue: English
• Weight: 930 KB
• Volume: 389
• Category: Article
• ISSN: 0028-0836
• DOI: 10.1038/39614

✦ Synopsis

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.