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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4871-4877. Prepublished online as a Blood First Edition Paper on February 15, 2005; DOI 10.1182/blood-2004-10-3888. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-3888v1 105/12/4871    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 Karim, M. Articles by Bushell, A. R. Search for Related Content PubMed PubMed Citation Articles by Karim, M. Articles by Bushell, A. R. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection: antigen-specific reactivation in vivo is critical for bystander regulation Mahzuz Karim, Gang Feng, Kathryn J. Wood, and Andrew R. Bushell From the Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom. The importance of CD25+CD4+ regulatory T (Treg) cells in the control of immune responses is established, but their antigen specificity in vivo remains unclear. Understanding Treg-cell specificity requirements will be important if their potential is to be developed for immunotherapy. Pretreatment of recipient mice with donor alloantigen plus anti-CD4 antibody generates CD25+CD4+ Treg cells with the capacity to prevent skin allograft rejection in adoptive transfer recipients. Here we demonstrate that, although this regulation can be antigen-specific, reactivation with the original tolerizing alloantigen allows the Treg cells to suppress rejection of third-party allografts. Aware of the limitations of alloantigen pretreatment, we asked whether graft-protective Treg cells could be generated against unrelated, nongraft antigens. We demonstrate that bystander regulation also extends to CD25+CD4+ Treg cells generated in vivo by exposure to nominal antigens under anti-CD4 antibody cover. Providing these Treg cells are reexposed to the tolerizing antigens before adoptive transfer, they prevent the rejection of fully allogeneic skin grafts. That this might form the basis of a clinically relevant tolerance induction strategy is demonstrated by the fact that, when combined with subtherapeutic anti-CD8 antibody, Treg cells generated in response to nongraft antigens facilitate the acceptance of cardiac allografts in primary recipients. (Blood. 2005;105:4871-4877) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. R. Guerin, J. R. Prins, and S. A. Robertson Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum. Reprod. Update, September 1, 2009; 15(5): 517 - 535. [Abstract] [Full Text] [PDF] C. Becker, C. Taube, T. Bopp, C. Becker, K. Michel, J. Kubach, S. Reuter, N. Dehzad, M. F. Neurath, K. Reifenberg, et al. Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells Blood, August 6, 2009; 114(6): 1263 - 1269. 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