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

Grimm, E.; Price, Z.; Bonavida, B.

Cellular Immunology 46(1): 77-99


ISSN/ISBN: 0008-8749
PMID: 314849
DOI: 10.1016/0008-8749(79)90247-8
Accession: 068526099

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Target cell destruction following contact of the target cell by specific alloimmune cytotoxic thymus-derived lymphocytes (CTL) was 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 showed that contact of the 2 cells resulted in tumor cell zeosis involving violent membrane blebbing and subsequent tumor cell death. TEM of the contact region showed that the CTL-tumor cell junction is extremely adherent. Examination of conjugates incubated at C to permit tumor cell lysis showed tumor cell membrane stretching and rupture, and tumor cell membrane fragments adhering to CTL. Close examination of the contact region revealed electron-lucent junctions spanning the gap between the 2 cell membranes, but no packaging or secretory apparatus was prominent. The results were consistent with the mechanism of cell-mediated cytolysis being a membrane phenomenon involving junctions connecting the CTL and target cell and the initial cell lesion observable as a stretching and rupture. The shear force of vigorous cell movements was most likely responsible for this target membrane tearing, creating a target cell lesion which results in loss of osmotic integrity and cell death.