Studies on the induction and expression of T cell-mediated immunity. VIII. Effector-target junctions and target cell membrane disruption during cytolysis

Target cell destruction following contact of the target cell by specific alloimmune cytotoxic thymus-derived lymphocytes (CTL) has been examined by time-lapse film (TLF), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Effector-target conjugates of murine CTL with leukemia cells were prepared for use in these studies. TLF shows that contact of the two cells results in tumor cell zeosis involving violent membrane blebbing, and subsequent tumor cell death. TEM of the contact region shows that the CTL-tumor cell junction is extremely adherent. Examination of conjugates incubated at 37 °C to permit tumor cell lysis shows tumor cell membrane stretching and rupture, and tumor cell membrane fragments adhering to CTL. Close examination of the contact region has revealed electron-lucent junctions spanning the gap between the two cell membranes, but no packaging or secretory apparatus was prominent. The results are consistent with the mechanism of cell-mediated cytolysis being a membrane phenomenon involving junctions connecting the CTL and target cell and the initial target cell lesion observable as a stretching and rupture. The shear force of vigorous cell movements is most likely responsible for this target membrane tearing, creating a target cell lesion which results in loss of osmotic integrity and cell death.