Coxsackievirus B-3 myocarditis. T-cell autoimmunity to heart antigens is resistant to cyclosporin-A treatment.

Abstract

A cardiotropic variant of coxsackievirus group B, Type 3 (CVB3) induces myocarditis in inbred Balb/c mice. Myocardial injury is predominantly mediated by T lymphocytes recognizing normal myocyte antigens, making this an autoimmune disease. Nonetheless, the autoimmune response cannot be inhibited by cyclosporin A (CSA) treatment of the infected animals. Mortality in treated mice was increased 2-4 times, but neither virus-specific antibody or cytolytic T-lymphocyte responses were affected, and maximal virus concentrations in the hearts of CSA-treated and control animals were similar. Cardiac damage remains T-cell-mediated, because mice given both CSA and rabbit anti-thymocyte serum (ATS) failed to develop significant myocardial inflammation. CSA did suppress immunity in Balb/c mice to an allogeneic C57B1 lymphoma, EL4. Subcutaneous inoculation of mice with 2.5 X 10(6) ascites tumor cells resulted in 100% of the CSA-treated animals having tumors averaging 340 mg 10 days later, compared with less than 10% of control animals having tumors averaging only 30 mg. Humoral immunity to the tumor was absent in CSA-treated mice. Therefore, whether CSA induces immunosuppression depends upon the antigenic stimulus used.