MECHANISM OF ANTIBODY-DEPENDENT NATURAL-KILLER CELL-MEDIATED AK-5 TUMOR-CELL DEATH

The mechanism of antibody-dependent natural killer (NK) cell-mediated killing of a histiocytic tumor, AK-5, was studied. In vitro exposure o f immune NK cells with antibody-primed AK-5 cells induced the formatio n of stable NK-AK-5 conjugates. The frequency of conjugate formation a fter 1 h coculture of immune NK cells was severalfold higher than that of normal cells. The occurrence of conjugate formation and the disint egration of conjugated targets only in the presence of anti-AK-5 antib ody revealed the antibody dependence in recognition, conjugate formati on, and triggering of lytic machinery leading to AK-5 cell death. Cocu lture of immune NK cells with AK-5 cells in the presence of anti-AK-5 antibody induced the expression of perforin mRNA as well as accumulati on of protein in the NK cells and extensive fragmentation of AK-5 cell DNA, thereby indicating the involvement of necrosis and apoptosis in the AK-5 cell death. The antibody-dependent expression of perforin as well as DNA fragmentation indicated these events to be consequent to E -T conjugate formation. The observation of target cell DNA fragmentati on revealed that the internal target disintegration is the first event which is followed by membrane damage leading to efficient tumor destr uction by the host immune system. (C) 1994 Academic Press, Inc.