MECHANISM OF INTERFERON GAMMA-INDUCED PROTECTION OF HUMAN GLIOSARCOMA CELLS FROM LYMPHOKINE-ACTIVATED KILLER LYSIS - DIVISION OF LYMPHOKINE-ACTIVATED KILLER-CELLS INTO NATURAL KILLER-LIKE AND T-LIKE CELLS

THE MECHANISM BY which interferon gamma (IFN-gamma) decreases the susceptibility of the established cultured gliosarcoma line GI-1 to lymphokine-activated killer (LAK) lysis was analyzed. The results of monolayer depletion and lectin-dependent cellular cytotoxicity assays by LAK cells revealed that the resistance to LAK lysis of IFN-gamma-treated GI-1 cells is manifested at the stage of LAK cell target recognition alone. We have also divided LAK cells into populations of phenotypically natural killer (NK)- and T-like cells with monoclonal antibodies and complement, respectively. We have used these cells to examine the mechanism of IFN-gamma-induced protection of GI-1 cells from LAK lysis in cold target inhibition, monolayer depletion, and direct binding assays. The results revealed that NK-like cells do not recognize IFN-gamma-treated GI-1 cells as efficiently as they do untreated targets, whereas T-like cells show the opposite tendency. In conclusion, we have demonstrated that the IFN-gamma induced protection of tumor cells from LAK lysis is predominantly regulated by the target recognition of NK-like cells. On the other hand, IFN-gamma-treated tumor cells may bind to T-like cells but fail to trigger them to initiate further stages for lysis as effectively as NK-like cells.