Immunopathogenesis of experimental Coxsackievirus induced myocarditis: role of autoimmunity.
The pathogenesis of cardiac injury in clinical myocarditis is unknown. Despite the association of the disease with recent viral infections, it is now assumed that immune rather than viral mechanisms are primarily responsible for myocyte destruction. Nonetheless, immunosuppressive therapy has not been universally effective in limiting myocardial damage. To better understand the mechanisms by which viral infections of the heart induce myocarditis, it has been necessary to resort to a murine model of the disease. When inbred Balb/c mice are infected with a cardiotropic variant of Coxsackievirus, group B, type 3 (CVB 3), the animals develop extensive interstitial and focal inflammatory cell infiltration of the heart similar to the lesions in humans. As in humans, a number of factors influence the severity of the disease. Males develop severe myocarditis while virgin females are generally protected. Female resistance does not persist during pregnancy, however, when resultant myocarditis is frequently worse than that observed in males. The susceptibility of males and pregnant females results from the influence of testosterone and progesterone on the immune response. Susceptible animals generate autoimmune cytolytic T lymphocytes which recognize normal myocyte cell surface antigens and are responsible for most of the cardiac damage in experimental myocarditis. Virgin females do not develop significant myocarditis apparently because the estrogens enhance suppressor cells which prevent the autoimmune T cell generation. Humoral (antibody-mediated) immunity to the heart antigens is also present, but apparently has no role in the pathogenesis of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Huber
S A
SA
Lyden
D C
DC
Lodge
P A
PA
D000818:Animals; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D001323:Autoantibodies; D012739:Gonadal Steroid Hormones; D007136:Immunoglobulins