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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-07-2157. This Article Full Text (PDF) All Versions of this Article: 2002-07-2157v1 101/2/621    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 Kuwana, M. Articles by Ikeda, Y. Search for Related Content PubMed PubMed Citation Articles by Kuwana, M. Articles by Ikeda, Y. Social Bookmarking                   What's this? Submitted July 19, 2002 Accepted December 31, 1969 Suppression of autoreactive T-cell response to glycoprotein IIb-IIIa by blockade of CD40/CD154 interaction: implications for treatment of immune thrombocytopenic purpura Masataka Kuwana*, Yutaka Kawakami, and Yasuo Ikeda Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan * Corresponding author; email: kuwanam{at}sc.itc.keio.ac.jp. The potential immunosuppressive effect of an anti-CD154 monoclonal antibody (mAb) on the pathogenic autoreactive T-cell response was evaluated using an in vitro culture system with glycoprotein IIb-IIIa (GPIIb-IIIa)-reactive T cells from patients with immune thrombocytopenic purpura (ITP). The anti-CD154 mAb did not inhibit T-cell proliferation, but suppressed anti-GPIIb-IIIa antibody production, in bulk peripheral blood mononuclear cell cultures stimulated with GPIIb-IIIa. Repeated antigenic stimulation of GPIIb-IIIa-reactive CD4+ T-cell lines in the presence of anti-CD154 mAb resulted in the loss of proliferative capacity and helper function for promoting anti-GPIIb-IIIa antibody production. These anergic T-cell lines showed a cytokine profile of low IFN- and high IL-10, and suppressed anti-GPIIb-IIIa antibody production. Our results indicate that blockade of the CD40/CD154 interaction induces generation of autoantigen-specific anergic CD4+ T cells with regulatory function, and could be a therapeutic option for suppressing pathogenic autoimmune responses in ITP patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Solanilla, J.-M. Pasquet, J.-F. Viallard, C. Contin, C. Grosset, J. Dechanet-Merville, M. Dupouy, M. Landry, F. Belloc, P. Nurden, et al. Platelet-associated CD154 in immune thrombocytopenic purpura Blood, January 1, 2005; 105(1): 215 - 218. [Abstract] [Full Text] [PDF] R. Stasi and D. Provan Management of Immune Thrombocytopenic Purpura in Adults Mayo Clin. Proc., April 1, 2004; 79(4): 504 - 522. [Abstract] [PDF] M. Kuwana, S. Nomura, K. Fujimura, T. Nagasawa, Y. Muto, Y. Kurata, S. Tanaka, and Y. Ikeda Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura Blood, February 15, 2004; 103(4): 1229 - 1236. [Abstract] [Full Text] [PDF]

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