2009 AWARDED GRANT
Jay Reddy, DVM, PhD
Delineating Autoimmunity in Postinfectious Myocarditis
University of Nebraska, Lincoln, NE
Jay Reddy, DVM, PhD – $308,000
Dilated cardiomyopathy (DCM) is a leading cause of death and heart transplants in children, due to the lack of effective treatments. Viral myocarditis induced by Coxsackievirus B3 (CVB3) is a common suspect in patients with DCM and the majority of them have elevated antibody levels to CVB3, but the attempts to demonstrate infectious viral particles have largely failed. Circulating antibodies have been demonstrated in patients with DCM to various antigens, including cardiac myosin suggesting that autoimmune response is an underlying mechanism for the development of DCM. It has long been debated whether the DCM occurs as a result of viral damage or a misdirected attack by the immune system. The study will use the mouse model of viral myocarditis induced with CVB3, which has features that mimic human disease to define the role of autoimmune response to the induction of postinfectious myocarditis. It is thought that myosin-reactive T-cells (lymphocytes) are generated during CVB3 infection and contribute to chronic inflammation. To address this hypothesis, class II reagents (tetramers) will be used to determine the generation and function of cardiac myosin and CVB3-specific or their cross-reactive T cells to induce myocarditis in susceptible mice. The use of tetramers will allow us to track the generation of antigen-specific T cells by fluorescence-activated cell sorting. Since CVB3-induced disease in mice is similar to that of humans, the proposed studies will provide new insights into the occurrence of post infectious cardiomyopathy, which will lay the foundation for new therapy to be targeted toward either virus or autoimmunity.