Effects of in vivo administration of anti-B7-1/B7-2 monoclonal antibodies on murine acute myocarditis caused by coxsackievirus B3

被引:37
作者
Seko, Y
Takahashi, N
Azuma, M
Yagita, H
Okumura, K
Yazaki, Y
机构
[1] Univ Tokyo, Fac Med, Dept Internal Med 3, Bunkyo Ku, Tokyo 113, Japan
[2] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan
[3] Asahi Life Fdn, Inst Adult Dis, Tokyo, Japan
关键词
immunology; T lymphocyte; infection; killer cell; cardiomyopathy;
D O I
10.1161/01.RES.82.5.613
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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, vie first analyzed the expression of B7-1/B7-2 in thr: 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-gamma). 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-gamma, 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.
引用
收藏
页码:613 / 618
页数:6
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