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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1018-1023. Prepublished online as a Blood First Edition Paper on October 6, 2005; DOI 10.1182/blood-2005-07-3032. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-3032v1 107/3/1018    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Coenen, J. J. A. Articles by Joosten, I. Search for Related Content PubMed PubMed Citation Articles by Coenen, J. J. A. Articles by Joosten, I. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells Jeroen J. A. Coenen, Hans J. P. M. Koenen, Esther van Rijssen, Luuk B. Hilbrands, and Irma Joosten From the Department of Bloodtransfusion and Transplantation Immunology and the Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. The immunosuppressive drugs rapamycin and cyclosporin A (CsA) are widely used to prevent allograft rejection. Moreover, they were shown to be instrumental in experimental models of tolerance induction. However, it remains to be elucidated whether these drugs have an effect on the CD4+CD25+ regulatory T-cell (TREG) population, which plays an important role in allograft tolerance. Recently, we reported that alloantigen-driven expansion of human CD4+CD25+ TREGs gives rise to a distinct highly suppressive CD27+TREG subset next to a moderately suppressive CD27-TREG subset. In the current study we found that rapamycin and CsA do not interfere with the suppressive activity of human naturally occurring CD4+CD25+ T cells. However, in contrast to CsA, rapamycin preserved the dominance of the potent CD27+TREG subset over the CD27-TREG subset after alloantigen-driven expansion of CD4+CD25+ TREGs in vitro. Accordingly, CD4+CD25+ TREGs cultured in the presence of rapamycin displayed much stronger suppressive capacity than CD4+CD25+ TREGs cultured in the presence of CsA. In addition, CD4+CD25+ TREG cells cultured in the presence of rapamycin, but not CsA, were able to suppress ongoing alloimmune responses. This differential effect of rapamycin and CsA on the CD27+TREG subset dominance may favor the use of rapamycin in tolerance-inducing strategies. 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