Our Research
Most healthy individuals have a propensity to develop autoimmune diseases, as evidenced by the presence of autoreactive T cells in their naïve periphery. T cells are educated in the thymus, where high-affinity T cell receptor (TCR)-bearing cells that interact with self-antigens are deleted by negative selection, while T cells with low-affinity TCR to self-antigens are selected positively and exported to the periphery. In spite of the presence of self-reactive T cells in the naïve peripheral repertoires, autoimmune responses do not ensue spontaneously. How this tolerance is maintained is a fundamental question. It has been suggested that the environmental antigens that bear similarities to self-antigens break self-tolerance by cross-reactivity. To this end, we focus our investigations on the identification of microbial products that can potentially induce autoimmunity in the heart and immunologically privileged sites such as the central nervous system and eyes through antigenic mimicry. Mechanistically, we are particularly interested in delineating the role of antigen-specific T cells in autoimmune diseases of infectious origin. We have generated the TCR transgenic mice for cardiac myosin 334-352, which allows us to determine the functionalities of CD4 and CD8 T cells within the single transgenic system. More recently, by using the single cell sequencing analysis, we have identified a major role for cytotoxic CD4 T cells in the development of viral myocarditis.
The long-term goal is to determine the mechanisms of viral cardiomyopathy that may lead to the development of effective prevention and therapeutic strategies. In that direction, we have identified a unique vaccine strain of Coxsackievirus B3 (CVB3) that offers cross-protection against multiple CVB serotypes such as CVB3 and CVB4, which are shown to be associated with viral cardiomyopathy and Type I Diabetes.