CYTOTOXICITY MEDIATED BY T-CELLS AND NATURAL-KILLER-CELLS IS GREATLY IMPAIRED IN PERFORIN DEFICIENT MICE

Perforin-deficient mice have been generated by homologous recombination to determine whether the effects of CD8(+) cytolytic T cells and natural killer cells are mediated by pore formation involving perforin. These mice are viable and fertile and have normal numbers of CD8(+) T cells and natural killer cells which do not lyse virus-infected or allogeneic fibroblasts or natural killer target cells in vitro. The mice fail to clear lymphocytic choriomeningitis virus and they eliminate fibrosarcoma tumour cells with reduced efficiency. Perforin is therefore a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis.