Peritoneal exudate cells harvested from mice after i.p. inoculation of 108 viable Bacillus Calmette-Guérin (BCG) organisms demonstrate vigorous lytic activity in vitro toward a large variety of target cells. Lytic activity was demonstrable within hours of BCG administration, was maximal after 4 to 5 days, and fell rapidly thereafter. Cell lysis observed in a 51Cr-release assay resulted from single events of collision with effector cells and was virtually complete within 4 hr. Effector cells were not found in the thymus or bone marrow, and the lytic activity of spleen and peripheral lymph nodes was only minimal. The effector cells were not induced by i.p. injection of thioglycollate medium or proteose peptone broth. Heat-killed BCG induced less activity than did viable BCG organisms.
The induction of lytic activity appeared to be under genetic control and to represent an amplification of a cell population present in the unstimulated animal. Some strains (CBA, B6C3F1) gave consistently high levels of of reactivity after BCG administration; others (A/J) showed much lower reactivity. Normal cells did not serve as targets for the BCG-induced effector cells, whereas tumor cells and long-term tissue culture cell lines were lysed. Susceptible targets included cells syngeneic, allogeneic, and xenogeneic to the effector cell source.
The rapid, vigorous lysis elicited by 4-day BCG-induced peritoneal exudates against a broad range of target cells indicates that the significance of this new cytotoxic phenomenon may be significant with respect to BCG immunotherapy.
This work was supported by Grants CA-19483 and AI-10280 from the National Institutes of Health and The Jane Coffin Childs Memorial Fund for Medical Research.
This is publication No. 276 from the O'Neill Memorial Research Laboratories, The Good Samaritan Hospital, Baltimore, Md.