NK cell-induced cytotoxicity is dependent on a Ca²⁺ increase in the target

In previous work we showed that programed cell death (PCD) in thymocytes is mediated by a sustained increase in cytosolic Ca²⁺ concentration, resulting in the activation of an endogenous endonuclease, DNA fragmentation, and cell death. In this study we investigated the roles of Ca²⁺ and DNA fragmentation in target cell killing by natural killer (NK) cells. The effector cells induced a rapid, sustained increase in cytosolic Ca²⁺ concentration in Jurkat target cells. Buffering the target cell cytosolic Ca²⁺ with the Ca²⁺-selective dye, quin-2, prevented target cell killing. Extensive DNA fragmentation was associated with killing in every target tested, and this response was also blocked by quin-2. The endonuclease inhibitor, aurintricarboxylic acid, inhibited both DNA fragmentation and killing without influencing the Ca²⁺ increase in target cells. Thus, it is concluded that NK cell killing depends on a Ca²⁺ increase and appears to involve endogenous endonuclease activation in target cells.