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Blood, 15 January 2008, Vol. 111, No. 2, pp. 680-687. Prepublished online as a Blood First Edition Paper on August 30, 2007; DOI 10.1182/blood-2007-07-101345. This Article Full Text (PDF) All Versions of this Article: blood-2007-07-101345v1 111/2/680    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 Ward, F. J Articles by Barker, R. N. Search for Related Content PubMed PubMed Citation Articles by Ward, F. J Articles by Barker, R. N. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 16, 2007 Accepted August 19, 2007 Clonal regulatory T cells specific for a red blood cell autoantigen in human autoimmune hemolytic anemia Frank J Ward*, Andrew M Hall, Lindsay S Cairns, Arabella S Leggat, Stanislaw J Urbaniak, Mark A. Vickers, and Robert N. Barker Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom Academic Transfusion Medicine Unit, Regional Transfusion Centre, Aberdeen, United Kingdom * Corresponding author; email: mmd475{at}abdn.ac.uk. Regulatory T (Tr) cells have the potential to treat immune-mediated disease, but cloning such cells for study from patients with autoimmune disease has proven difficult. Here, we describe autoantigen-specific, IL-10 secreting Tr cell clones recovered ex vivo from a patient with autoimmune hemolytic anemia (AIHA) and characterize their phenotype, origin and regulatory function. These IL-10+ Tr cells recognized a peptide, 71H-85L, derived from the RhD red blood cell autoantigen and shared phenotypic characteristics with both natural and inducible Tr. The clones also expressed different Tr markers depending on activation state: high levels of CD25 and LAG-3 when expanding non-specifically, but FoxP3 after activation by the autoantigen they recognize. Despite a discrete Tr phenotype these cells stably expressed the Th1 signature transcription factor T-bet suggesting they derive from Th1 T cells. Finally, the contribution of CTLA-4 in activating these IL-10+ Tr cells, was confirmed by analysing responses to transgenic B7.1 like molecules that preferentially bind either CD28 or CTLA-4. Overall, these Tr cells have a functional phenotype different from those described in previous studies of human Tr populations, which have not taken account of antigen specificity, and understanding their properties will enable them to be exploited therapeutically in AIHA. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Unraveling the immune response during AIHA Neil D. Avent Blood 2008 111: 483. [Full Text] [PDF] 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]

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