CYTOTOXIC LYMPHOCYTE ACTIVITY IN RHEUMATIC HEART DISEASE (RHD)

Abstract

Decreased peripheral blood lymphoproliferative response due to dysfunctional non-T lymphocytes and the presence of unusual antigenie structures on peripheral blood non-T cells are among the alterations in the immune system found in patients with rheumatic cardiac valvular disease. The present study examined natural killer cell activity and generation of cytotoxic lymphocytes after exposure to bklastogen A in patients with RHD and age- and socioeconomic-matched controls with recurrent tonsillitis but no rheumatic history, signs or symptoms. Peripheral blood mononuclear cells (PBMNC) were obtained by isopycnic centrifugation. Fresh PBMNC were incubated with 4 concentrations of K562 erythroleukemia cell targets. Rates of target cell lysis were measured by assay of lactate dehydrogenase using a spectrophotometric assay. Natural cytotoxic activity of freshly isolated PBMNC did not differ between RHD and controls. However, the PBMNC from RHD showed significantly less cytotoxicity after they were cultured alone in media for 6 days. In marked contrast, when cultured for 6 days in the presence of streptococcal blastogen A, PBMNCs from RHD showed greater rates of target cell lysis than controls at all target cell concentrations (P<.01 at 8 x 104 target cells). Thus, PBMNCs from RHD patients after exposure to a purified group A streptococcal product generate markedly greater than normal cytotoxicity against a target that displays differentiation antigens but not major histocompatibility antigens on its surface.