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Interleukin 10 is a growth factor for a population of regulatory T cells
  1. Nuffield Dept of Surgery,
  2. University of Oxford,
  3. John Radcliffe Hospital,
  4. Oxford OX3 9DU, UK

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A hallmark of the intestinal immune system is its ability to mount a rapid and potent effector response to pathogenic bacteria, viruses and parasites, while remaining tolerant to the vast array of luminal bacteria and ingested antigens. It is generally considered that the breakdown of this tolerance is of crucial importance in the development of inflammatory bowel disease (IBD) in humans. The mechanisms governing immune responsiveness and non-responsiveness in the intestine are not well understood; however, the recent finding that IBD develops in mice which lack particular T cell subsets (severe combined immunodeficient (SCID) mice restored with CD45RBhigh CD4+ T cells1 ,2 and T cell receptor-α chain deficient mice3 ), or in mice with targeted deletions of the interleukin (IL)-10 (IL-10KO)4 or IL-2 (IL-2KO)5 genes suggests that T cell subsets and cytokines play an active role in regulating potentially tissue damaging immune responses in the intestine. Although these models may seem complex and arcane to clinical gastroenterologists, several broad themes have emerged from these studies which may be of tremendous clinical importance.

The paper by Groux et al sheds some light on how IL-10 (generally thought of as an immunosuppressive cytokine) may act to regulate intestinal inflammation. The authors show that repetitive antigenic stimulations in vitro of human and murine CD4+ cells in the presence of IL-10 results in the generation of a T cell subset with low proliferative capacity which secretes high levels of IL-10 and interferon γ (IFN-γ) and has immune regulatory activities both in vitro and in vivo. These cells, which the authors term T regulatory 1 cells (Tr1), exhibit a cytokine profile distinct from …

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