The Journal of Experimental Medicine
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A correction to this article has been published: J. Exp. Med. 196 (6) 867
A correction to this article has been published: J. Exp. Med. 196 (4) 559
Published 15 July 2002. doi:10.1084/jem.20020642
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© Rockefeller University Press, 0022-1007/2002/7/247/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 2, July 15, 2002 247-253

Brief Definitive Report

Human CD4+CD25+ Regulatory, Contact-dependent T Cells Induce Interleukin 10–producing, Contact-independent Type 1-like Regulatory T Cells

Detlef Dieckmann, Cord Henrik Bruett, Heidi Ploettner, Manfred Bernhard Lutz and Gerold Schuler

Department of Dermatology, University Hospital of Erlangen, 91052 Erlangen, Germany

Address correspondence to Gerold Schuler, Dept. of Dermatology, University Hospital of Erlangen-Nuremberg Hartmannstrasse 14, 91052 Erlangen, Germany. Phone: 49-9131-85-1006; Fax: 49-9131-85-6175; E-mail: schuler{at}derma.imed.uni-erlangen.de

It has been recently demonstrated that regulatory CD4+CD25+ CD45RO+ T cells are present in the peripheral blood of healthy adults and exert regulatory function similar to their rodent counterparts. It remains difficult to understand how the small fraction of these T cells that regulate via direct cell-to-cell contact and not via secretion of immunosuppressive cytokines could mediate strong immune suppression. Here we show that human CD4+CD25+ T cells induce long-lasting anergy and production of interleukin (IL)-10 in CD4+CD25- T cells. These anergized CD4+CD25- T cells then suppress proliferation of syngenic CD4+ T cells via IL-10 but independent of direct cell contact, similar to the so-called type 1 regulatory T (Tr1) cells. This ‘catalytic’ function of CD4+CD25+ T cells to induce Tr1-like cells helps to explain their central role for the maintenance of immune homeostasis.

Key Words: regulatory T cells • human • immune tolerance • anergy • IL-10


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