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Autoimmune Mechanisms in Viral Myocarditis
Abstract
Viral myocarditis induced by Coxsackievirus 3 (CVB3) is commonly employed as a disease model to investigate autoimmune events in the development of dilated cardiomyopathy. Human isolates of CVB3 induce myocarditis in susceptible mouse strains, and the disease course is manifested mainly as viral and post-viral phases that have resemblance to human disease. Although, evidence exists to support a notion that autoimmunity can be a component of CVB3 pathogenesis, mechanistic basis for the generation of autoreactive T cell responses, including cross-reactive T cells, if any, is poorly understood. In this research, we tested a hypothesis that CVB3 infection leads to the generation of autoreactive T cells with multiple antigen-specificities that can contribute to viral pathogenesis. First, for comprehensive evaluation of autoreactive T cell responses, we needed to characterize T cell epitopes for two cardiac antigens namely, β1-adrenergic receptor and adenine nucleotide translocator 1. Second, by addressing the molecular mimicry hypothesis, we found no evidence for cross-reactive T cell responses to be generated in CVB3 infection for selected antigens. Third, by evaluating antigen-specific T cell responses, we observed that T cells specific to cardiac antigens importantly, myosin heavy chain-α and sarcoplasmic/endoplasmic reticulum calcium ATPase 2a to be detected consistently. Finally, unexpectedly, cardiac reactive T cells were detected in the liver, suggesting that liver can potentially act as a reservoir for autoreactive cells to be recirculated in infected animals. Taken together, our data provide an experimental evidence that autoreactive T cells with multiple antigen-specificities can be generated as a secondary event to the primary damage caused by the virus that may have therapeutic implications.
Subject Area
Immunology
Recommended Citation
Basavalingappa, Rakesh Halekote, "Autoimmune Mechanisms in Viral Myocarditis" (2018). ETD collection for University of Nebraska-Lincoln. AAI10743299.
https://digitalcommons.unl.edu/dissertations/AAI10743299