Cell-Mediated Cytotoxicity in Hearts With Dilated Cardiomyopathy: Correlation With Interstitial Fibrosis and Foci of Activated T Lymphocytes

Objectives. The purpose of this study was to investigate the expression of perforin and T-cell intracellular antigen-1, two crucial components of lymphocyte-mediated cytotoxicity, in endomyocardial biopsies from patients with idiopathic dilated cardiomyopathy. Background. Previous reports have demonstrated the presence of myocardial interstitial fibrosis and increased infiltrating lymphocytes in patients with dilated cardiomyopathy. However, the pathogenic significance of these lymphocytic infiltrates remains unclear. Methods. Endomyocardial biopsies from 134 patients with idiopathic dilated cardiomyopathy were histologically and immunohistologically analyzed. Monoclonal antibodies against diverse T-lymphocyte antigens, perforin and T-cell intracellular antigen-1 were used with the highly sensitive avidin–biotin complex technique. Positive cells were counted in at least 10 high power fields. Results. Perforin and T-cell intracellular antigen-1 were immunohistologically detected in all biopsies. Immunoreactivity was restricted to the cytoplasm and was granular in nature, indicating specific staining of cytoplasmic granules. Correlations were established between the expression of perforin and T-cell intracellular antigen-1 and the abundance of foci of various T-lymphocyte subpopulations and, most importantly, the degree of interstitial fibrosis on routine histologic examination (p = 0.015). Conclusions. Cytotoxic activity is clearly present in endomyocardial biopsies from patients with idiopathic dilated cardiomyopathy. Local activation—that is, focal accumulation of T lymphocytes—seems to be important for the generation of lymphocyte-mediated cytotoxicity. The interstitial fibrosis commonly seen in dilated cardiomyopathy may be caused by cytotoxic T-lymphocyte damage to the myocardium.