Killing of normal cells by activated mouse natural killer cells: Evidence for two patterns of genetic regulation of lysis

Abstract

Normal primary mouse thymocytes and peritoneal cells are sensitive for lysis by mouse spleen cells activated by in vivo infection with lymphocytic choriomeningitis virus (LCMV). With both thymocytes and peritoneal cells as targets, the active killer cell seemed to be an NK cell, as judged by high activity in the mouse mutant nude and low activity in the mouse mutant beige. Thymocytes from 1- to 3-week-old mice were found to be most NK-sensitive, while peritoneal cells showed highest sensitivity for lysis when harvested from older (6- to 8-week-old) animals. In a direct comparison the genetic regulation of NK activity against thymocytes and peritoneal cells was analyzed. The same strain origin of both target cells and effector cells in either system was used. With thymocytes as target cells, spleen cells from LCMV-infected C3H/St mice invariably showed the highest activity closely followed by cells from the BALB/c strain, while the SWR/J and the A/J strains both were considerably less reactive. The same pattern of high- or low-reactive strains was seen regardless of the genotype of the thymocyte target donor, and the same pattern of cytotoxicity was also seen against the YAC-I lymphoma target. An entirely different genetic regulation was active in the lysis of peritoneal cells, where a unique pattern of reactivity was seen for each effector cell genotype, dependent on the strain origin of the peritoneal target cell. In line with previous findings, syngeneic combinations of effector-target cells yielded little or no reactivity, while various allogeneic combinations showed considerable levels of activity. Also, primary cultures of embryonic fibroblasts were used as target cells. The genetics of the fibroblast target system was more similar to that seen in the thymocyte-YAC-I assay since no evidence for a preferential killing of allogeneic target cells was seen.