Effects of In Vivo Administration of Anti–B7-1/B7-2 Monoclonal Antibodies on Murine Acute Myocarditis Caused by Coxsackievirus B3

From the Third Department of Internal Medicine (Y.S., N.T., Y.Y.), Faculty of Medicine, University of Tokyo; the Department of Immunology (Y.S., M.A., H.Y., K.O.), School of Medicine, Juntendo University, Tokyo, Japan; and the Institute for Adult Diseases (Y.S.), Asahi Life Foundation, Tokyo, Japan.

Correspondence to Yoshinori Seko, MD, Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7–3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

Abstract—In viral myocarditis, we previously reported that antigen-specific T cells infiltrate the heart and play an important role in the pathogenesis of myocardial damage. For antigen-specific T-cell activation to occur, it is necessary for T cells to receive costimulatory signals provided by costimulatory molecules expressed on antigen-presenting cells as well as main signals provided by binding of T-cell receptors to antigens. To investigate the roles of costimulatory molecules B7-1 and B7-2 in the development of acute viral myocarditis, we first analyzed the expression of B7-1/B7-2 in the hearts of mice with acute viral myocarditis induced by coxsackievirus B3 (CVB3). Second, we evaluated the induction of B7-1/B7-2 in cultured cardiac myocytes treated with interferon gamma (IFN-). Third, we examined the effects of in vivo administration of anti–B7-1/B7-2 monoclonal antibodies (mAbs) on the development of acute viral myocarditis. We found that CVB3-induced murine acute myocarditis resulted in enhanced expression of B7-1/B7-2 in cardiac myocytes. The expression of B7-1/B7-2 in cardiac myocytes could be induced in vitro by IFN-. We found that in vivo anti–B7-1 mAb treatment markedly decreased myocardial inflammation, whereas anti–B7-2 mAb treatment abrogated the protective effect of anti–B7-1. Our findings indicate that distinct roles for B7-1 and B7-2 antigens are involved in the development of acute viral myocarditis and raise the possibility of immunotherapy with anti–B7-1 mAb to prevent T-cell–mediated myocardial damage in viral myocarditis.

Key Words: immunology • T lymphocyte • infection • killer cell • cardiomyopathy

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