Evidence that protein kinase C activation is essential for killing by IL-2-activated lymphocytes

Previous pharmacological evidence has suggested that activation of protein kinase C (PKC) is necessary for T and natural killer (NK) killing of different target cells. In the present study we find, using interleukin 2 (IL-2)-activated lymphocytes (LAK cells), that phosphorylation of a well-characterized 80-kDa PKC substrate increases during conjugation to target cells. Furthermore, down-regulation of PKC by pretreatment with the active phorbol esters PDB (24 h) or PMA (2 h), but not with the inactive phorbolester PDD, simultaneously inhibits killing by LAK cells. H-7, an inhibitor of PKC, also inhibited LAK-cell killing without affecting the target-effector cell conjugate formation. We also demonstrate that pretreatment of target cells with phorbol ester (PMA) decreases killing, suggesting that PKC activation in the target cell population may also influence killing although the effect may vary depending on the particular target cell used. We conclude that PKC activation is essential for triggering of lysis in LAK cells.