Chronic myocarditis induced by T cells reactive to a single cardiac myosin peptide: persistent inflammation, cardiac dilatation, myocardial scarring and continuous myocyte apoptosis.
Recent recognition that an autoimmune myocarditis may precede, and result in, dilated cardiomyopathy has focused attention on immune mechanisms of myocardial injury. In this paper, we describe a model of chronic autoimmune myocarditis in the Lewis rat. The production of myocarditis has been previously described by this group and in brief is accomplished by a single tail vein infusion of activated T cells specific for a 17-amino acid peptide from rat cardiac myosin. In this report, animals were followed for approximately 6 months post-T-cell infusion. Hearts from animals which received cardiac myosin specific T cells all showed extensive fibrosis associated with ongoing inflammation. Apoptosis, identified by TdT-mediated dUTP nick end labelling (TUNEL), was identified as a mode of myocyte death in hearts with acute and chronic myocarditis but not in age- and sex-matched controls. Immunohistochemistry was used to characterize the immune infiltrate and adhesion molecules in hearts with chronic myocarditis and these findings were compared to hearts with acute myocarditis. We propose that this rat model of chronic myocarditis mimics human disease, since inflammation results in ventricular dilatation and myocyte hypertrophy reminiscent of dilated cardiomyopathy. This model offers potential for further investigation of immune, functional and possible therapeutic aspects of autoimmune related cardiomyopathies.
Ratcliffe
N R
NR
Department of Pathology, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA.
Hutchins
J
J
Barry
B
B
Hickey
W F
WF
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000166:cytology; D009218:Myosins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D016177:Macrophage-1 Antigen; D010446:Peptide Fragments; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009218:Myosins