Non-specific induction of cytotoxicity in normal human lymphocytes in vitro: studies of mechanism and specificity of the reaction

Abstract

The cytotoxic effect of non-immunized human lymphocytes was investigated in a system where the lymphocytes were applied to fibroblast monolayers of different genotypes. Non-immunized lymphocytes were not cytotoxic, disregarding the target cell genotype provided that the lymphocyte suspensions were free from contaminating granulocytes. By adding phytohaemagglutinin (PHA) to the culture, the lymphocytes became strongly cytotoxic and exerted their effect already after 4–8 hr. Cytotoxicity was shown to develop independently of other expressions of PHA-stimulation of the lymphocyte, such as RNA-, protein- and DNA-syntheses and morphological transformation. Living lymphocytes were required for cytotoxicity to occur and heating the lymphocytes to 48·5°C, ultrasound disintegration or freezing-thawing abolished their ability to damage the target cells. The PHA-induced cytotoxicity was equally expressed on allogeneic and autochthonous fibroblasts. Analogous results were obtained when the lymphocytes were stimulated by streptolysin O or anti-lymphocyte serum. The results suggest that expression of cytotoxicity is an immunologically non-specific process, caused by stimulated lymphocytes. When the lymphocytes have acquired a cytotoxic potential they do not discriminate between the target cell genotype or the event triggering lymphocyte cytotoxicity. The specificity of the cellular immune reactions is probably confined to the immunological recognition step initiating the cytotoxic potential. This recognition step is by-passed if the lymphocytes are stimulated by PHA or other non-specific stimulators.