Suppression and abrogation of suppression of induced nonspecific cytotoxicity against tumor cells.

Fresh spleen cells obtained from normal mice of various strains including athymic mice and NK-less beige mice were found to suppress in a H-2-nonrestricted manner nonspecific cytotoxic activity of in vitro-cultured normal mouse spleen cells or that of nonadherent peritoneal exudate cells from mice treated with Propionibacterium acnes. Natural killer-insensitive MM2 ascites tumor cells were used as the target of assay of the cytotoxicity. The suppressive activity of fresh spleen cells was not affected by elimination of glass-adherent cells and of Thy-1.2-positive cells but partly decreased after removal of Sephadex G-10- or nylon wool-adherent cells. The suppressive activity of the cells seemed to be mediated, at less partly, by a soluble factor (or factors) which was released by fresh spleen cells into medium during short term culturing. The suppressive factor was a heat-resistant, dialyzable material which was stable at wide range of pH. Cells did not produce the factor at low temperature and its production was insensitive to indomethacin. Long term culture supernatant of spleen cells contained the suppressive factor and a relatively unstable high molecular weight substance which abrogated its activity. The characteristics of the cells which produced such desuppressive factor seemed to be identical to those of the induced cytotoxic effector cells. Kinetical analyses indicated that these two factors influenced, directly or indirectly, cytolytic activity of the effector cells without changing binding affinity between the effector and the target.