In vitro cytotoxicity by human lymphocytes from individuals immunized against histocompatibility antigens. I. Kinetics and specificity of the reaction. Influence of metabolic inhibitors and anti-lymphocyte serum.

Lymphocytes from humans that had rejected allogeneic skin grafts acquired a cytotoxic potential, which was expressed upon contact with fibroblast monolayer cultures of the skin donor genotype. No cytotoxic effect was obtained on autochthonous fibroblasts, but did occur on other allogeneic fibroblasts, non-related to the skin donor, suggesting shared histocompatibility antigens. The damage to the target cells developed at the area of lymphocyte application and was detected after 48 hr. The cytotoxic effect of the immune lymphocytes on the specific target cells was suppressed by treatment with actinomycin-C, Mitomycin-C and prednisolone, indicating that cellular synthetic processes and cell divisions are required for cytotoxicity to be expressed. Anti-lymphocyte serum also inhibited the cytotoxic reaction, probably by coating the lymphocyte surface. In view of previous investigations, concerning cytotoxicity exerted by non-immunized lymphocytes stimulated by non-specific agents, the present results suggest that the specificity of the cytotoxic damage by immunized lymphocytes is confined to the initial immunological recognition of the antigen(s) on the target cells. This reaction triggers the lymphocytes to a cytotoxic state which can be non-specifically expressed. The need for synthetic processes within the lymphocytes may be required for magnifying the process by increasing the number of cytotoxically activated cells and probably also for the continuous synthesis of the antigen-specific receptors.