Coxsackievirus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens.
Male Balb/c mice inoculated with a heart-adapted variant of Coxsackievirus, group B, type 3 (Nancy) (CVB3M), develop extensive myocarditis and cytolytic activity to primary cultures of uninfected and infected myocytes. To elucidate the mechanisms of myocyte injury in myocarditis, two distinct cytolytic T-lymphocyte (CTL) populations were isolated by immunoadsorption of lymph node cells to glutaraldehyde-fixed uninfected and infected myocyte monolayers. One population preferentially adsorbed to and lysed uninfected myocytes (autoreactive CTLs), while the other adsorbed to and lysed CVB3M-infected myocytes (virus-specific CTL). Neither CTL population adsorbed to monolayers of HeLa, L929, or umbilical cord endothelial cells, or to myocytes infected with a related but nonmyocarditic Coxsackievirus B-3 variant ( CVB3o ). While both autoreactive and virus-specific CTLs induced myocarditis in vivo, the lesions caused by autoreactive CTLs were more extensive and necrotizing than those of virus-specific cells. These results support the hypothesis that CVB3 -induced myocarditis results, in part, from autoimmunity to myocyte antigens.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000276:immunology*; D029822:Enterovirus B, Human; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000941:Antigens; D001323:Autoantibodies; D001324:Autoantigens