LYSIS OF MURINE MACROPHAGES BY LYMPHOKINE-ACTIVATED KILLER-LIKE CELLS INDUCED BY BCG INVITRO

The lymphokine-activated killer (LAK)-like activity was found to be induced in mouse splenocytes cultured together with Bacillus Calmette-Guerin (BCG). The killer cells induced by BCG were capable of killing both NK-sensitive (YAC-1, P388D1) and NK-resistant (P815) tumor cells. As an important finding, they also lysed syngeneic macrophages (M-phi). The anti-M-phi killer activity appeared on day 2, and reached a peak on day 5 of culture. Phenotype analysis of the killer cells by depletion techniques using monoclonal antibody (mAb) and complement indicated that the majority of these anti-M-phi killer cells were Thy-1+ and asiolo GM1+. This M-phi cytolysis could be inhibited by the addition of cold M-phi, YAC-1 tumor cells, and P815 tumor cells, suggesting that the same population of the effector cells recognize M-phi and tumor cells. The addition of anti-MHC class I, anti-MHC class II, anti-L3T4, or anti-Ly-2 mAb directly to assay cultures did not affect anti-M-phi cytolysis, suggesting that the MHC molecules are not involved in the cytolysis of M-phi by the BCG-induced killer cells. The addition of anti-LFA-1 mAb partially inhibited the cytotoxicity, suggesting importance of the contact between targets and effectors in the cytolysis. Our present data suggest that activation of murine lymphocytes with BCG induces LAK-like cells capable of killing a wide variety of tumor cells as well as M-phi and this anti-M-phi cytolysis is mediated by nonspecific killer cells.