RESTRICTED USAGE OF T-CELL RECEPTOR V-ALPHA-V-BETA GENES IN INFILTRATING CELLS IN THE HEARTS OF PATIENTS WITH ACUTE MYOCARDITIS AND DILATEDCARDIOMYOPATHY

Prolonged myocardial cell damage initiated by acute myocarditis is tho ught to be one of the most important etiology of dilated cardiomyopath y, To investigate the immunological mechanisms involved in the pathoge nesis of dilated cardiomyopathy, we analyzed the phenotypes of infiltr ating cells and examined the expression of perforin in infiltrating ce lls in the hearts of patients with dilated cardiomyopathy as well as a cute myocarditis. We also examined the expression of HLA and intercell ular adhesion molecule-1 (ICAM-1) in myocardial tissue of these patien ts, Furthermore, to evaluate the antigen specificity of infiltrating T cells and persistence of viral genomes in the myocardial tissue, we a nalyzed the expression of T cell receptor (TCR) V alpha and V beta gen es as well as enterovirus genomes by PCR, We found infiltration of per forin-expressing killer cells and enhanced expression of HLA class I a nd 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, in dicating that a specific antigen in the hearts was targeted, Because n o enterovirus genomes were detected in all patients, it is strongly su ggested that a cell-mediated autoimmune mechanism triggered by virus i nfection may play a critical role in the pathogenesis of dilated cardi omyopathy. However, we could not exclude the possibility that viruses other than enteroviruses could be pathogenic in these patients.