On the mode of action of intravesical bacillus Calmette-Guérin: in vitro characterization of BCG-activated killer cells.

Previously we had shown that, upon activation with viable bacillus Calmette-Guérin (BCG), peripheral blood mononuclear cells (PBMNC) could be rendered cytotoxic against otherwise insensitive natural killer (NK)-resistant bladder cancer cell lines. This phenomenon had been termed the BCG-activated killer (BAK) cell phenomenon. By means of depletion and enrichment procedures of mononuclear cell subpopulations derived from BCG-activated PBMNC we further characterized the cytolytic BAK effector cells functionally in an in vitro cytotoxicity assay against the bladder carcinoma cell line BT-A and phenotypically in their pathway of activation. Neither macrophages nor CD4+ T-helper/inducer cells exerted cytotoxic BAK activity. This cytotoxicity was restricted to the CD8+CD56+ subpopulation of T-cytotoxic/NK cells. Furthermore, activation of BAK cells via interferon gamma (IFN-gamma) was evidenced by the complete inhibition of BAK cell generation with an IFN-gamma antibody.