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Science 26 August 1994: Vol. 265. no. 5176, pp. 1225 - 1227 DOI: 10.1126/science.7520604
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Articles
Science, Vol 265, Issue 5176, 1225-1227
Copyright © 1994 by American Association for the Advancement of Science
Treatment of murine lupus with CTLA4Ig
BK Finck,
PS Linsley,
and
D Wofsy
Department of Medicine, University of California, San Francisco.
The interaction of B7-related molecules on antigen-presenting cells with CD28 or CTLA-4 antigens on T cells provides a second signal for T cell activation. Selection inhibition of the B7-CD28 or B7-CTLA-4 interactions produces antigen-specific T cell unresponsiveness in vitro and suppresses immune function in vivo. To determine whether selective inhibition of the B7-CD28 or B7-CTLA-4 interactions could suppress spontaneous autoimmune disease, a B7-binding protein was generated by genetic fusion of the extracellular domain of murine CTLA-4 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody (muCTLA4Ig). In lupus-prone NZB/NZW filial generation (F1) mice, treatment with muCTLA4Ig blocked autoantibody production and prolonged life, even when treatment was delayed until the most advanced stage of clinical illness. These findings suggest a possible role for human CTLA4Ig in the treatment of autoimmune diseases in humans.
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