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The Journal of Immunology, 2006, 177: 2775-2783.
Copyright © 2006 by The American Association of Immunologists, Inc.

CD103 Is a Marker for Alloantigen-Induced Regulatory CD8+ T Cells

Elena Uss1,*,§, Ajda T. Rowshani§, Berend Hooibrink{dagger}, Neubury M. Lardy{ddagger}, René A. W. van Lier* and Ineke J. M. ten Berge§

* Department of Experimental Immunology and {dagger} Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, The Netherlands; {ddagger} HLA-Diagnostics Laboratory, Sanquin, Amsterdam, The Netherlands; and § Division of Nephrology, Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

The {alpha}Ebeta7 integrin CD103 may direct lymphocytes to its ligand E-cadherin. CD103 is expressed on T cells in lung and gut and on allograft-infiltrating T cells. Moreover, recent studies have documented expression of CD103 on CD4+ regulatory T cells. Approximately 4% of circulating CD8+ T cells bear the CD103 molecule. In this study, we show that the absence or presence of CD103 was a stable trait when purified CD103 and CD103+CD8+ T cell subsets were stimulated with a combination of CD3 and CD28 mAbs. In contrast, allostimulation induced CD103 expression on ~25% of purified CD103CD8+ T cells. Expression of CD103 on alloreactive cells was found to be augmented by IL-4, IL-10, or TGF-beta and decreased by addition of IL-12 to MLCs. The alloantigen-induced CD103+CD8+ T cell population appeared to be polyclonal and retained CD103 expression after restimulation. Markedly, in vitro-expanded CD103+CD8+ T cells had low proliferative and cytotoxic capacity, yet produced considerable amounts of IL-10. Strikingly, they potently suppressed T cell proliferation in MLC via a cell-cell contact-dependent mechanism. Thus, human alloantigen-induced CD103+CD8+ T cells possess functional features of regulatory T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Address correspondence and reprint requests to Dr. Elena Uss, Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, L1-110, 1105 AZ Amsterdam, The Netherlands. E-mail address: a.uss{at}amc.uva.nl

2 Abbreviations used in this paper: Treg, T regulatory cell; Tr1, T regulatory 1; pen/strep, penicillin/streptomycin; Tc, T cytotoxic.




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