Specific and nonspecific antitumor immunity. II. Macrophage-mediated nonspecific effector activity induced by BCG and...

The recently described inhibition of DNA synthesis (IDS) assay, which measures antitumor effector (E) cell function by the quantitation of decreases in tritiated thymidine incorporation of target tumor cells, was used to analyze the nonspecific effector activity of peritoneal exudate cells (PEC) from mice infected intraperitoneally with BCG. These PEC could inhibit growth of and then kill all tumor target (effector to target) cells tested at E/T ratios as low as 1:1. This activity was not due to alterations in media, nor could any activity be shown for cell-free supernatants prepared from active cells. The principal cell type mediating this effector function was the "activated" macrophage-no activity was found in lymphoid or polymorphonuclear leukocytes. Direct effector to target contact was necessary for the cytotoxic reaction. The time course of these effects and comparative 51Cr release data were reported. The removal of the adherent nonspecific effectors from PEC of mice immunized to both BCG and a specific syngeneic tumor revealed a specific cytotoxicity of the remaining lymphoid cells. These results indicated that nonspecific effector activity by "activated" macrophages induced by BCG infection could be a potent antitumor mechanism, at least in vitro, and the IDS assay provided an accurate, reproducible, and quantitative method for measurement of the function of such E cells.