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© The Rockefeller University Press, 0022-1007/1999/10/995/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 7, October 4, 1999 995-1004

An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation

Chrystelle Assemana, Smita Mauzeb, Michael W. Leachc, Robert L. Coffmanb, and Fiona Powriea
a Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom
b DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304
c Schering-Plough Research Institute, Lafayette, New Jersey 07848

Correspondence to: Fiona Powrie, Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. Tel:44-1865-221482 Fax:44-1865-768876 E-mail:fiona.powrie{at}nds.ox.ac.uk.

A T helper cell type 1–mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RBhigh CD4+ T cells and can be prevented by cotransfer of the CD45RBlow subset. The immune-suppressive activities of the CD45RBlow T cell population can be reversed in vivo by administration of an anti-transforming growth factor ß antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RBlow population. This population isolated from IL-10–deficient (IL-10-/-) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti–murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RBlow CD4+ cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RBhigh CD4+ cells, as CD45RBlow CD4+ cells from WT mice were able to inhibit colitis induced by IL-10-/- CD45RBhigh CD4+ cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.

Key Words: interleukin 10, inflammatory bowel disease, CD4+ T lymphocyte, regulatory T lymphocyte


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