680 RESISTANCE OF CULTURED CHORIOCARCINOMA CELLS TO CYTOTOXIC LYMPHOCYTES

Cultured choriocarcinoma cells (BeWo) exist which share many of the morphologic and biosynthetic properties of normal human trophoblasts.In an attempt to develop a model for the immunologic relationship between mother and fetus, we mixed BeWo cells with mitogen-activated cytotoxic lymphocytes in vitro. Microscopic observations revealed that BeWo cells exhibited a marked resistance to the cytolytic effects of the activated lymphocyte in spite of 24 hour exposure and intimate cell to cell contact. The control target cells, a line of human hepatoma cells, were readily destroyed. A quantitative cytotoxicity assay was devised which involved measuring the residual radioactivity of 3-H-Thymidine prelabeled target cells following exposure to activated lymphocytes. Employing this assay, we confirmed the morphologic results and showed that BeWo cells were resistant to the cytotoxic effects of lymphocytes activated by phytohemagglutinin, pokeweed, and allogeneic cells in mixed lymphocyte cultures. Moreover, BeWo were resistant to injury over a wide range of killer to target cell ratios. Significant killing of the BeWo cells occurred only after prolonged exposure (48 and 72 hours) to the activated lymphocytes. Exposing the target cells briefly to trypsin augmented the killing of control cells but not BeWo. These observations suggest that one mechanism which may assist the fetus (or a choriocarcinoma) in its immunologic survival is the intrinsic resistance of trophoblast to lymphocyte mediated cytotoxicity.