Autoimmunity in coxsackievirus infection.
Abstract Viral infections frequently result in the production of autoantibodies. In most cases, these autoantibodies are low-affinity IgMs that exhibit extensive cross-reactions. Sometimes these virus-triggered immune responses progress to a pathogenic autoimmunity to form autoimmune disease. To delineate the mechanisms determining induction of autoimmune disease, we have investigated in detail a model of autoimmune myocarditis induced in genetically susceptible mice by infection with a cardiotropic strain of coxsackievirus B3. We found that the autoimmune sequelae of the viral infection can be simulated by immunization of the susceptible mice with murine cardiac myosin. In both models of the disease, the determination of whether to progress from a contained viral myocarditis to a pathogenic autoimmune response is made within hours after induction of infection and is characterized by production of a few key cytokines, including IL-1beta and TNFalpha. Many of the lessons learned from study of these models are applicable to human myocarditis and dilated cardiomyopathy.
Rose
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NR
Johns Hopkins Center for Autoimmune Disease Research, Johns Hopkins University, 615 N. Wolfe St., E5009, Baltimore, MD 21205, USA. nrrose@jhmi.edu
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D024722:Cardiac Myosins / Q000276:immunology* / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D009205:Myocarditis / Q000276:immunology* / Q000821:virology; D009569:Nitric Oxide / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001323:Autoantibodies; D009569:Nitric Oxide; D003165:Complement System Proteins; D024722:Cardiac Myosins