Autoimmune cardiac-specific T cell responses in dilated cardiomyopathy.
Dilated cardiomyopathy (DCM) is a common cause of congestive heart failure and commonly occurs in the setting of autoimmune cardio-inflammatory processes. Consistent with this notion myocardial damage and dilatory remodeling consistent with DCM occurs upon adoptive transfer of T cell subsets reactive to self-antigens abundantly expressed in cardiac tissue. In this review we discuss etiologic mechanisms by which cardio-destructive T cells are generated during T cell ontogeny, and we review accumulated work identifying myocardial-derived T cell epitopes. Additionally, we describe several possible mechanisms whereby autoimmune T cell responses are sustained during chronic DCM. Epitope spreading, intra-cardiac persistence of pathogen-derived proteinaceous determinants, and generation of long-lived memory T cells are discussed as putative processes operative in the chronic maintenance of DCM.
Jane-wit
Daniel
D
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA. ddj@po.cwru.edu
Tuohy
Vincent K
VK
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D009154:Mutation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D000096927:AIRE Protein
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D014157:Transcription Factors; D000096927:AIRE Protein