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Blood, 15 January 2005, Vol. 105, No. 2, pp. 735-741. Prepublished online as a Blood First Edition Paper on September 28, 2004; DOI 10.1182/blood-2003-11-3900. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3900v1 105/2/735    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 Balandina, A. Articles by Berrih-Aknin, S. Search for Related Content PubMed PubMed Citation Articles by Balandina, A. Articles by Berrih-Aknin, S. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis Anna Balandina, Sandrine Lécart, Philippe Dartevelle, Abdelhadi Saoudi, and Sonia Berrih-Aknin From the Laboratoire de Physiologie Thymique, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 8078, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Service de Chirurgie thoracique, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Institut National de la Santé et de la Recherche Médicale U-563, Centre de Physiopathologie, Toulouse-Purpan, Toulouse, France. Thymus-derived CD4+CD25+ regulatory T (Treg) cells are essential for the maintenance of immunologic self-tolerance. Despite their critical role in the active suppression of experimental autoimmune disorders, little is known about their involvement in human autoimmune diseases. Myasthenia gravis (MG) is a CD4+ T cell–dependent autoimmune disease and the thymus is assumed to be the initiation site. To identify possible defects in the Treg cells in MG, we analyzed CD4+CD25+ cells in thymi from patients with MG compared to those from healthy subjects. We found a normal CD4+CD25+ number but a severe functional defect in their regulatory activity together with a decreased expression of the transcription factor, Foxp3, which is essential for T-cell regulatory function. The phenotypic analysis of CD4+CD25+ thymocytes revealed an increased number of activated effector cells with strong Fas expression in patients with MG. However, whatever their level of Fas, CD4+CD25+ thymocytes from patients with MG remained unable to suppress the proliferation of responding cells, indicating that the impaired Treg cell function is not due to contamination by activated effector T cells. These data are the first to demonstrate a severe functional impairment of thymic Treg cells in MG, which could contribute to the onset of this autoimmune disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Grant, U. Oh, K. Yao, Y. Yamano, and S. Jacobson Dysregulation of TGF-{beta} signaling and regulatory and effector T-cell function in virus-induced neuroinflammatory disease Blood, June 15, 2008; 111(12): 5601 - 5609. [Abstract] [Full Text] [PDF] M.-L. Chen, B.-S. Yan, Y. Bando, V. K. Kuchroo, and H. L. 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