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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-05-1383. This Article Full Text (PDF) All Versions of this Article: 2002-05-1383v1 100/13/4529    most recent Alert me when this article is cited Alert me if a correction is posted 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 Hall, A. M Articles by Barker, R. N Search for Related Content PubMed PubMed Citation Articles by Hall, A. M Articles by Barker, R. N Social Bookmarking                   What's this? Submitted May 13, 2002 Accepted July 17, 2002 Interleukin-10 mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen Andrew M Hall, Frank J Ward, Mark A Vickers, Lisa-Marie Stott, Stanislaw J Urbaniak, and Robert N Barker* Medicine and Therapeutics, University of Aberdeen, Aberdeen, Scotland, United Kingdom; Academic Transfusion Medicine Unit, Regional Transfusion Centre, Aberdeen, Scotland, United Kingdom Medicine and Therapeutics, University of Aberdeen, Aberdeen, Scotland, United Kingdom * Corresponding author; email: r.n.barker{at}abdn.ac.uk. Regulatory T-cells have been shown to control animal models of immune-mediated pathology by inhibitory cytokine production, but little is known about such cells in human disease. Here we characterize regulatory T-cell responses specific for a human red blood cell autoantigen in patients with warm-type autoimmune hemolytic anemia. Peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia were found either to proliferate and produce interferon-, or to secrete the regulatory cytokine interleukin-10, when stimulated in vitro with a major red blood cell autoantigen, the RhD protein. Flow cytometric analysis confirmed that the majority of the responding cells were of the CD4+ phenotype. Serial results from individual patients demonstrated that this bias towards proliferative or interleukin-10 responses was unstable over time, and could reverse in subsequent samples. Epitope mapping studies identified peptides from the sequence of the autoantigen that preferentially induced interleukin-10 production, rather than proliferation, and demonstrated that many contain naturally processed epitopes. Responses to such peptides suppressed T-cell proliferation against the RhD protein, an inhibition that was mediated largely by interleukin-10 and dependent on CTLA-4 costimulation. Antigenic peptides with the ability to stimulate specific regulatory cells may represent a new class of therapeutic agents for immune-mediated disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Serafini, M. Andreani, M. Testi, M. Battarra, A. Bontadini, E. Biral, K. Fleischhauer, S. Marktel, G. Lucarelli, M. G. Roncarolo, et al. Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia Haematologica, October 1, 2009; 94(10): 1415 - 1426. [Abstract] [Full Text] [PDF] A. D'Ambrosio, M. Colucci, O. Pugliese, F. Quintieri, and M. Boirivant Cholera toxin B subunit promotes the induction of regulatory T cells by preventing human dendritic cell maturation J. Leukoc. Biol., September 1, 2008; 84(3): 661 - 668. [Abstract] [Full Text] [PDF] P. Szodoray, B. Nakken, S. Barath, J. Gaal, M. Aleksza, M. 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