Culture and characterization of lymphocytic infiltrates from endomyocardial biopsies of patients with idiopathic myocarditis

Abstract

Immune reactions are thought to be of primary importance in the pathogenesis of idiopathic myocarditis and dilated cardiomyopathy in humans. Based on the experimental data and histological findings, we have hypothesized that infiltrating T lymphocytes are a key element in the pathogenesis of myocarditis. In order to obtain infiltrating T lymphocytes from myocardium for study, we subjected tissue from 169 consecutive non-transplant endomyocardial biopsies from 135 patients to tissue culture in the presence of human recombinant interleukin 2 (rIL2). Overall, 40 (24%) biopsies from 33 patients gave rise to CD3+ cells. Phenotyping of 31 expanded cultures was performed by flow cytometry and revealed 19 CD4+ predominant cultures, and CD8+ predominance in the remaining 12. Sixteen of the expanded lymphocyte cultures were tested for lymphokine production and all produced IL2 and a macrophage-stimulating factor (ILO) in varying amounts. Each of 14 cultures tested demonstrated variable degrees of cytotoxicity against NK-target K562 cells and an NK-resistant tumour cell line. Neither the amount of lymphokine production nor the degree of cytotoxicity correlated with the phenotypic predominance of the cultures. Thus activated T lymphocytes can be derived from human endomyocardial biopsies, and these cells are capable of being stimulated and expanded in vitro. Although their specificity remains to be determined, myocardially derived T lymphocytes are probably intimately related to the pathogenesis of myocarditis.