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.
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)-gamma 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-gamma 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.
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan. sekoyosh-tky@umin.ac.jp
Y
Y
Seko
N
N
Takahashi
H
H
Yagita
K
K
Okumura
M
M
Azuma
Y
Y
Yazaki
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis / Q000276:immunology*; D051940:B7-2 Antigen; D002311:Cardiomyopathy, Dilated / Q000276:immunology / Q000628:therapy / Q000821:virology; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000628:therapy*; D029822:Enterovirus B, Human; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000276:immunology / Q000628:therapy / Q000821:virology*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D007371:Interferon-gamma