In vivo significance of T cells in the development of Coxsackievirus B3 myocarditis in mice. Immature but antigen-specific T cells aggravate cardiac injury.
Acute myocardial damage similar to that seen in human myocarditis occurs in BALB/c mice after infection with coxsackievirus B3 (CB3) or encephalomyocarditis virus (EMC). To investigate the role of antigen-specific T cells in the pathogenesis of this disorder, we compared CB3 disease expression in T cell-deficient, athymic nude (nu/nu) mice, in heterozygote (nu/+) mice with normal T cell function, and in nu/nu mice reconstituted with spleen cells from CB3- or EMC-infected nu/+ mice. Acute myocarditis occurred in both nu/nu and nu/+ mice. Severe myocarditis, however, developed only in nu/+ and nu/nu mice reconstituted with CB3-sensitized T cells, but not in those reconstituted with EMC-sensitized T cells. Myocardial virus titer and serum anti-CB3 antibody production were similar in nu/+ and nu/nu groups. Additionally, the presence of Thy 1.2 (pan T), Ly 1 (precursor of other T cell subsets), and Ly 2 (suppressor/cytotoxic T) positive cells was demonstrated in the myocardium in nu/+ and nu/nu mice reconstituted with CB3-sensitized T cells, but not with T cells sensitized by another virus, EMC. These results indicate that immature but antigen-specific T cells play a role in the pathogenesis of ongoing myocarditis.
Charles A. Dana Research Institute, Boston, Mass.
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Kishimoto
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Abelmann
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology; D029822:Enterovirus B, Human / Q000276:immunology; D000939:Epitopes; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009205:Myocarditis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000914:Antibodies, Viral; D000939:Epitopes