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

Nature volume 389, pages 737–742 (1997)Cite this article

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 tolerance1. 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+CD45RBhighsplenic 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 .

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Figure 1: Generation of murine Tr1 cells in the presence of IL-10.
Figure 2: Proliferative responses of Tr1 cells.
Figure 3: Tr1 cells inhibit the antigen-specific proliferative responses of naive CD4+T cells.
Figure 4: Co-transfer of Tr1 clones prevents colitis.

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Acknowledgements

We thank E. Murphy, E. Callas and D. Polakoff for technical assistance; R. L. Coffman and L. L. Lanier for reviewing the manuscript; and J. A. Katheiser for secretarial help. DNAX Research Institute of Molecular and Cellular Biology, Inc. is supported by Schering-Plough Corporation.

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  1. Jan E. de Vries

    Present address: Novartis Research Institute, Brunner Strasse 59, A-1235, Wien, Austria

  2. Maria Grazia Roncarolo

    Present address: Department of Pediatrics, Regina Margherita Children's Hospital, University of Torino, Piazza Polonia 94, 10126, Torino, Italy

Authors and Affiliations

  1. Human Immunology Department, DNAX Research Institute of Molecular and Cellular Biology, Inc., 901 California Avenue, Palo Alto, 94304-1104, California, USA

    Hervé Groux, Anne O'Garra, Mike Bigler, Matthieu Rouleau & Svetlana Antonenko

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Groux, H., O'Garra, A., Bigler, M. et al. A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737–742 (1997). https://doi.org/10.1038/39614

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