The involvement of protein kinase C in activation-induced cell death in T-cell hybridoma.

T-cell hybridoma activated by a variety of stimuli such as anti-cell surface antigen, notably CD3 and T-cell receptors, and Con A undergoes a cell lysis process called activation-induced cell death (AICD). It was found that the major protein kinase C (PKC) isoform in the 2B4.11 T-cell hybridoma, PKC(alpha), was translocated from the cytosolic to the particulate fraction when these hybridoma cells were induced to die by plastic-adsorbed anti-CD3 antibodies. Inhibitors of protein phosphorylation rescued 2B4.11 cells from AICD as determined by the analysis of cellular metabolism and the proportion of living cells. Furthermore, PKC(alpha) down-regulation by phorbol ester treatment abolished AICD, and the degree of PKC down-regulation correlated well with the degree of AICD abolishment, suggesting that PKC activation represents an essential step in the molecular mechanisms underlying AICD in this T-cell hybridoma.