Target cell lysis: ultrastructural and cytoskeletal alterations

Abstract

The cytoskeleton, with particular emphasis on filamentous actin (f-actin), was studied in target L cells treated with the cytotoxic lymphokine, alpha-lymphotoxin (LT), or with cytotoxic T lymphocytes. The f-actin distribution was also examined in cytotoxic T cells interacting with targets. LT-treated targets retracted their processes, rounded up, and subsequently underwent lysis. These changes were accompanied by loss of stress fibers and rearrangement of f-actin, although there was no appreciable change of total cytoskeletal protein or f-actin content. Thus, the arrangement of f-actin was altered, but not its cellular concentration. Similar morphologic changes were seen at the light microscopic level in targets affected by T cells. T lymphocytes interacting with targets showed marked polarization of f-actin adjacent to the effector target interface; some f-actin rearrangement was also noted in the underlying target cell cytoplasm. Ultrastructurally, the LT-affected targets showed a decrease of f-actin organization within microvilli and underneath the plasma membrane associated with loss of villi and cytoplasmic bleb formation. Furthermore, prominent bundles of intermediate filaments were apparent and clusters of vesicles were noted which may be an expression of plasma membrane repair. These findings suggest that target cell cytoskeletal changes may lead to the morphologic changes in LT- and T cell-mediated cytotoxicity and lysis.