Cellular and molecular mechanisms of murine autoimmune myocarditis.
Dilated cardiomyopathy is a prevalent cause of progressive heart disease and sudden death, and most patients with cardiomyopathy have a history of viral myocarditis. Coxsackie B3 (CB3) picornaviruses can be detected in as many as 50% of these patients and CB3 infections have been epidemiologically linked to chronic heart disease. Several clinical and experimental studies suggest that chronic stages of disease are mediated by an autoimmune response against heart muscle myosin. Human heart disease can be mimicked in mice using cardiac myosin as autoantigen. Murine cardiac myosin-induced myocarditis is an organ-specific autoimmune disease and mediated by CD4+ T cells that recognize a myosin-specific peptide in association with MHC class II molecules. Here, the recent discovery of autoimmune epitopes derived from the alpha isoform of cardiac myosin, the functional roles of surface receptor and signal transduction molecules, and the molecular mechanisms of target organ susceptibility will be discussed.
Penninger
J M
JM
Amgen Institute/Ontario Cancer Institute, Department of Medical Biophysics, Toronto, Canada.
Pummerer
C
C
Liu
P
P
Neu
N
N
Bachmaier
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D016827:CD8 Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009218:Myosins / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D009218:Myosins