Lack of specificity for viral and H-2 antigens by anomalous T killer cells generated in murine leukocyte cultures.

Mouse spleen cells, cultivated in vitro for 6 days in the presence or absence of syngeneic irradiated virus-induced tumor cells, lysed a variety of virus-induced tumor cells and normal cells in a long (19-hr) 51Cr-release cytotoxicity assay. Little or no specificity for viral or H-2 antigens was detected. This anomalous killing (AK) activity contrasted with H-2-restricted cytotoxic T lymphocyte (CTL) activity generated in secondary mixed leukocyte-tumor cell cultures and detected in a short (4- to 6-hr) 51Cr-release assay. Studies of competitive inhibition by unlabeled target cells in the long assay suggested that AK effectors were a broadly heterogeneous mixture of cells representing many clones, each recognizing a different antigenic determinant. AK effector cells shared properties with CTL: they could be generated from spleen cells of natural killer cell-deficient mice bearing the beige mutation but not from those of T cell-deficient nude mice; they expressed Thy-1 and Lyt-2 antigens; and they were nonphagocytic. AK activity could be generated from normal spleen cells of mice of all inbred strains examined, but the levels of activity generated varied in a strain-specific manner and were not significantly influenced by H-2 genotype.