The Journal of Experimental Medicine
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Published online 4 June 2001.
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© The Rockefeller University Press, 0022-1007/2001/6/1303/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 11, June 4, 2001 1303-1310

Brief Definitive Report

Ex Vivo Isolation and Characterization of CD4+CD25+ T Cells with Regulatory Properties from Human Blood

Detlef Dieckmanna, Heidi Plottnera, Susanne Berchtolda, Thomas Bergera, and Gerold Schulera
a Department of Dermatology, University of Erlangen-Nuremberg, 91052 Erlangen, Germany

Correspondence to: Gerold Schuler, Department of Dermatology, University of Erlangen-Nuremberg, Hartmannstrasse 14, 91052 Erlangen, Germany. Tel:49-9131-853-3661 Fax:49-9131-853-6175 E-mail:schuler{at}derma.med.uni-erlangen.de.

It has been known for years that rodents harbor a unique population of CD4+CD25+ "professional" regulatory/suppressor T cells that is crucial for the prevention of spontaneous autoimmune diseases. Here we demonstrate that CD4+CD25+CD45RO+ T cells (mean 6% of CD4+ T cells) are present in the blood of adult healthy volunteers. In contrast to previous reports, these CD4+CD25+ T cells do not constitute conventional memory cells but rather regulatory cells exhibiting properties identical to their rodent counterparts. Cytotoxic T lymphocyte–associated antigen (CTLA)-4 (CD152), for example, which is essential for the in vivo suppressive activity of CD4+CD25+ T cells, was constitutively expressed, and remained strongly upregulated after stimulation. The cells were nonproliferative to stimulation via their T cell receptor for antigen, but the anergic state was partially reversed by interleukin (IL)-2 and IL-15. Upon stimulation with allogeneic (but not syngeneic) mature dendritic cells or platebound anti-CD3 plus anti-CD28 the CD4+CD25+ T cells released IL-10, and in coculture experiments suppressed the activation and proliferation of CD4+ and CD8+ T cells. Suppression proved IL-10 independent, yet contact dependent as in the mouse. The identification of regulatory CD4+CD25+ T cells has important implications for the study of tolerance in man, notably in the context of autoimmunity, transplantation, and cancer.

Key Words: CD4+CD25+ T cells, regulatory T cells, immune tolerance, anergy, dendritic cells


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