Effects of in vivo administration of anti-B7-1/B7-2 monoclonal antibodies on murine acute myocarditis caused by coxsackievirus B3.
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-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.
Seko
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Takahashi
N
N
Azuma
M
M
Yagita
H
H
Okumura
K
K
Yazaki
Y
Y
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis / Q000276:immunology*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000276:immunology*; D029822:Enterovirus B, Human; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology; D009205:Myocarditis / Q000276:immunology* / Q000628:therapy / Q000821:virology; D009206:Myocardium / Q000737:chemistry / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins