Restricted usage of T cell receptor V alpha-V beta genes in infiltrating cells in the hearts of patients with acute myocarditis and dilated cardiomyopathy.
Prolonged myocardial cell damage initiated by acute myocarditis is thought to be one of the most important etiology of dilated cardiomyopathy. To investigate the immunological mechanisms involved in the pathogenesis of dilated cardiomyopathy, we analyzed the phenotypes of infiltrating cells and examined the expression of perforin in infiltrating cells in the hearts of patients with dilated cardiomyopathy as well as acute myocarditis. We also examined the expression of HLA and intercellular adhesion molecule-1 (ICAM-1) in myocardial tissue of these patients. Furthermore, to evaluate the antigen specificity of infiltrating T cells and persistence of viral genomes in the myocardial tissue, we analyzed the expression of T cell receptor (TCR) V alpha and V beta genes as well as enterovirus genomes by PCR. We found infiltration of perforin-expressing killer cells and enhanced expression of HLA class I and ICAM-1 in the myocardial tissue. We also found that the repertoires of TCR V alpha as well as V beta gene transcripts were restricted, indicating that a specific antigen in the hearts was targeted. Because no enterovirus genomes were detected in all patients, it is strongly suggested that a cell-mediated autoimmune mechanism triggered by virus infection may play a critical role in the pathogenesis of dilated cardiomyopathy. However, we could not exclude the possibility that viruses other than enteroviruses could be pathogenic in these patients.
Seko
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ishiyama
S
S
Nishikawa
T
T
Kasajima
T
T
Hiroe
M
M
Kagawa
N
N
Osada
K
K
Suzuki
S
S
Yagita
H
H
Okumura
K
K
D000208:Acute Disease; D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology* / Q000821:virology; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004770:Enterovirus / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016679:Genome, Viral; D006680:HLA Antigens / Q000032:analysis; D006321:Heart / Q000821:virology; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007694:Killer Cells, Natural; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000150:complications / Q000276:immunology / Q000473:pathology* / Q000821:virology; D009206:Myocardium / Q000473:pathology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000737:chemistry; D014777:Virus Diseases / Q000276:immunology / Q000473:pathology* / Q000821:virology
D006680:HLA Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin; D018799:Intercellular Adhesion Molecule-1