Decreased natural killer (NK) susceptibility of human NK target cells after phosphatidylinositol-specific phospholipase C treatment.

Phosphatidylinositol-specific phospholipase C (PI-PLC) treatment of the human natural killer (NK) target cells Molt-4, Jurkat, and U937 reduced their susceptibility to killing by human NK cells in a dose-dependent fashion. This indicates that a cell surface structure, anchored by a glycosyl-phosphatidylinositol (G-PI) moiety, is important in NK cytotoxicity. In contrast, another common NK target cell line, K562, remained susceptible to NK killing after enzyme treatment, suggesting that distinct target structures are expressed by this cell line. PI-PLC treatment of Molt-4 cells also reduced their sensitivity to human lymphokine activated killer (LAK) cells, suggesting that NK and LAK cells share common specificity in the killing of Molt-4. In contrast, PI-PLC had no effect on the killing of the LAK target cell line, Daudi, which is only weakly sensitive to unactivated NK cells. Killing of a variety of murine target cells by murine NK cells was not affected by PI-PLC treatment, but cross-species killing of Molt-4 by murine NK cells was inhibited by PI-PLC, suggesting a common mechanism in the killing of this human target cell line. The PI-PLC treatment of effector cells from either species did not reduce their NK activity. The reduction in sensitivity of the Molt-4, Jurkat, and U937 target cells probably results from a loss of a target specific G-PI linked membrane molecule, but other possible explanations for these results are also discussed.