ACTIVATION-INDUCED APOPTOSIS IN JURKAT CELLS THROUGH A MYC-INDEPENDENT MECHANISM

Apoptosis can be induced in the human leukemic T-cell line Jurkat when these cells are stimulated by several known T-cell activators. Among the stimuli that activate Jurkat cells, calcium ionophore A23187, phyt ohemagglutinin and cross-linked monoclonal antibody anti-CD3 are the b est inducers of apoptosis. The activator of protein kinase C phorbol-1 2,13-dibutyrate causes a rapid but transient stimulation of DNA fragme ntation and cell death, and soluble monoclonal antibody anti-CD3 has n o effect. Furthermore, apoptosis is delayed when Jurkat cells are stim ulated simultaneously with calcium ionophore and phorbol ester. We hav e analysed the mechanism underlying the induction of apoptosis by thes e agents and found that down-regulation of c-myc expression by pretrea tment with the DNA binding antibiotic mithramycin, an inhibitor of c-m yc transcription, does not prevent the activation of the apoptotic pro cess. In the light of these results we can conclude that in these leuk emic T-cells, activation of apoptosis may occur by a mechanism indepen dent of c-myc expression.