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Prepublished online as a Blood First Edition Paper on May 29, 2003; DOI 10.1182/blood-2003-04-1164. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1164v1 102/6/2180    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 Jiang, S. Articles by Lechler, R. I. Search for Related Content PubMed PubMed Citation Articles by Jiang, S. Articles by Lechler, R. I. Related Collections Immunobiology Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2180-2186 IMMUNOBIOLOGY Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo Shuiping Jiang, Niels Camara, Giovanna Lombardi, and Robert I. Lechler From the Department of Immunology, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom. Although CD4+CD25+ regulatory T cells are pivotal in the prevention of autoimmunity and appear to mediate transplantation tolerance, little is known concerning their antigen specificity. Here we describe the induction of a human CD4+CD25+ regulatory T-cell line specific for a defined peptide alloantigen (human leukocyte antigen A2 [HLA-A2] 138-170) by priming purified CD4+CD25+ cells ex vivo. The regulatory cells were anergic and retained their ability to suppress antigen-driven responses of CD4+CD25– cells. They inhibited not only interleukin 2 (IL-2) secretion by CD4+CD25– T cells specific for the same peptide but also direct alloresponse of naive CD4+CD25– T cells stimulated by semiallogeneic dendritic cells (DCs) in the presence of the peptide ("linked suppression"). They also suppressed the response of CD4+ T cells specific for viral and bacterial antigens. The suppressive T-cell line showed sustained high CD25 expression. These findings suggest that peripheral CD4+CD25+ regulatory cells are a precommitted cell lineage from which cells with specificity for non–self-peptides can be selected. This may pave the way for inducing and expanding peptide antigen-specific regulatory T cells ex vivo for cell therapy in transplantation, allergy, and autoimmune disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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