Experimental autoimmune myocarditis and its pathomechanism.
The pathomechanisms of autoimmune myocarditis are quite different from viral infection. In this type of myocarditis, cardiac myosin fragments, proper dendritic cells and autoreactive T cells are the 3 major elements in initiating and promoting the inflammation. The causative epitope is locating on the S2 rod portion of the myosin heavy chain (MHC). Through our recombinant study, the peptide was found to be located on the latter half of MHC residues 1070 to 1165. Activity of antigenicity was not different between alpha and beta chain. The cardiac dendritic cell presents a unique structure with large mononuclear and interdigitating processes. This antigen presenter is quickly activated and suppressed by the antigen. The autoreactive T cell is closely linked with cytokine production. In the initial stage of myocarditis, IL-2 and IL-12 are increased. According to the progression of inflammatory changes, a great amount of IL-1b, INF-gamma and TNF-alpha is released around the diseased tissue. At the same time, NO is massively produced from infiltrating macrophages. Cytokines secreted from inflammatory cells accelerate T cell induction from Th0 to Th1. In the convalescent stage, production of TGF-beta 1 and IL-10 become dominant. They contribute to cell induction from Th0 to Th2.
Izumi
T
T
Department of Internal Medicine, Kitasato University, Sagamihara, Japan. izumi@med.kitasato-u.ac.jp
Takehana
H
H
Matsuda
C
C
Yokoyama
H
H
Kohno
K
K
Suzuki
K
K
Inomata
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D006801:Humans; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D018995:Myosin Heavy Chains / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D016207:Cytokines; D000939:Epitopes; D018995:Myosin Heavy Chains