The Journal of Experimental Medicine
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Published online 4 June 2001.
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© The Rockefeller University Press, 0022-1007/2001/6/1285/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 11, June 4, 2001 1285-1294

Original Article

Identification and Functional Characterization of Human Cd4+Cd25+ T Cells with Regulatory Properties Isolated from Peripheral Blood

Helmut Jonuleita, Edgar Schmittb, Michael Stassenb, Andrea Tuettenberga, Jurgen Knopa, and Alexander H. Enka

a Department of Dermatology, University of Mainz, D-55101 Mainz, Germany
b Institute of Immunology, University of Mainz, D-55101 Mainz, Germany
Dept. of Dermatology, University of Mainz, D-55101 Mainz, Langenbeckstr. 1, Germany.49-6131-17550549-6131-173541

jonuleit{at}hautklinik.klinik.uni-mainz.de

A subpopulation of peripheral human CD4+CD25+ T cells that expresses CD45RO, histocompatibility leukocyte antigen DR, and intracellular cytotoxic T lymphocyte–associated antigen (CTLA) 4 does not expand after stimulation and markedly suppresses the expansion of conventional T cells in a contact-dependent manner. After activation, CD4+CD25+ T cells express CTLA-4 on the surface detectable for several weeks. These cells show a G1/G0 cell cycle arrest and no production of interleukin (IL)-2, IL-4, or interferon (IFN)-{gamma} on either protein or mRNA levels. The anergic state of CD4+CD25+ T cells is not reversible by the addition of anti-CD28, anti–CTLA-4, anti–transforming growth factor β, or anti–IL-10 antibody. However, the refractory state of CD4+CD25+ T cells was partially reversible by the addition of IL-2 or IL-4. These data demonstrate that human blood contains a resident T cell population with potent regulatory properties.

Key Words: human regulatory T cells • CD4+CD25+ T cells • CTLA-4 expression • T cell inhibition • tolerance

Abbreviations used in this paper: CTLA, cytotoxic T lymphocyte–associated antigen; DC, dendritic cell; HLA, histocompatibility leukocyte antigen; HSA, human serum albumin; RT, reverse transcription.

© 2001 The Rockefeller University Press


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