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Effects of in vivo administration of anti‐B7‐1/B7‐2 monoclonal antibodies on the survival of mice with chronic ongoing myocarditis caused by Coxsackievirus B3
Author(s) -
Seko Yoshinori,
Takahashi Naoyuki,
Yagita Hideo,
Okumura Ko,
Azuma Miyuki,
Yazaki Yoshio
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199905)188:1<107::aid-path319>3.0.co;2-7
Subject(s) - myocarditis , monoclonal antibody , in vivo , coxsackievirus , administration (probate law) , antibody , medicine , immunology , virology , biology , virus , enterovirus , political science , genetics , law
In acute myocarditis and dilated cardiomyopathy, it has previously been reported that antigen‐specific T‐cells infiltrate the heart and play an important role in the myocardial damage involved. For antigen‐specific T‐cell activation to occur, it is necessary for the T‐cell to receive co‐stimulatory signals provided by co‐stimulatory molecules expressed on the antigen‐presenting cell (APC), as well as the main signal provided by binding of the T‐cell receptor (TCR) to the antigen. To investigate the roles for the co‐stimulatory molecules B7‐1 and B7‐2 in the development of chronic ongoing viral myocarditis, firstly the expression of B7‐1/B7‐2 was analysed in the hearts of A/J mice with myocarditis induced by Coxsackievirus B3 (CVB3). Secondly the induction of B7‐1/B7‐2 on cultured cardiac myocytes treated with interferon (IFN)‐γ was evaluated. Thirdly the effects of the in vivo administration of anti‐B7‐1/B7‐2 monoclonal antibodies (MAbs) on the survival of mice with viral myocarditis were examined. CVB3‐induced myocarditis resulted in enhanced expression of B7‐1/B7‐2 on cardiac myocytes. The expression of B7‐1/B7‐2 on cardiac myocytes could be induced by IFN‐γ in vitro . In vivo anti‐B7‐1 MAb treatment significantly prolonged the survival of mice with myocarditis, whereas anti‐B7‐2 MAb treatment abrogated the protective effect of anti‐B7‐1. These findings indicate that distinct roles for B7‐1 and B7‐2 antigens are involved in the development of viral myocarditis and raise the possibility of immunotherapy with anti‐B7‐1 MAb to prevent T‐cell‐mediated cardiac myocyte injury and to improve the prognosis of viral myocarditis. Copyright © 1999 John Wiley & Sons, Ltd.