Inhibition of natural killer cell activity by a soluble substance released by rat peritoneal cells

We describe here a soluble substance released by nonadherent cells from the peritoneal cavity of W/Fu rats that markedly inhibits the activity of mouse, rat, and human natural killer (NK) cells. The NK-inhibiting substance (NK-IS) has low molecular weight (less than 1000), is heat resistant (100 degrees for 15 min), and is insensitive to nonspecific proteases. NK-IS is produced in the presence of indomethacin (1 to 10 micrograms/ml), suggesting it is not prostaglandin. The inhibitory effect was seen on unstimulated as well as on cells activated in vivo or in vitro by Corynebacterium parvum. The activity of cells mediated antibody-dependent cell cytotoxicity (K-cells) was also inhibited by NK-IS although to a lesser degree. In sharp contrast, the substance had little effect on lysis mediated by murine or human cytotoxic T-lymphocytes. Production of NK-IS from rat peritoneal cells was significantly greater than by spleen cells. since the peritoneal cavity is relatively deficient in base-line NK activity compared to spleen, these data suggest that NK-IS may play an in vivo role in the expression of NK cytotoxicity.