Coxsackieviruses are closely associated with clinical myocarditis as a probable etiological agent. The association is usually circumstantial, however, since virus is only rarely isolated from myocarditis patients. The general inability to isolated virus, the appearance of the lesions, the long clinical course of the disease and the positive response of some patients to immunosuppressive therapy suggest an autoimmune element to the disease. A murine model of myocarditis using a highly myocarditic strain of Coxsackievirus Group B type 3 (CVB3M) and inbred Balb/c mice has been developed. As in humans infectious virus is rapidly eliminated from the heart while cardiac inflammation and necrosis persists. It is the immune T lymphocyte which causes the majority of the cardiac injury. Dinstinct cytolytic T lymphocytes to uninfected and to CVB3M infected myocytes have been identified and designated autoreactive CTL and virus specific CTL respectively. While both CTL populations cause myocarditis, preliminary work indicates that cardiac injury caused by the autoreactive CTL is more extensive and severe.
The specific aims of this proposal are to fully characterize the nature of the cardiac injury caused by both autoreactive and virus specific CTL as to morphology and kinetics of lesion formation. Elucidation of the extent of autoimmunity in viral myocarditis will also be possible by administration of autoreactive CTL to uninfected mice or to mice weeks or months after initial infection and elimination of the virus. Studies will also focus on the role of suppressor cells in preventing and limiting autoimmune myocarditis. This investigation should serve as a foundation in determining the immunopathologic processes in CVB3 myocarditis.
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