Susceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the proliferative status of the target

The data presented suggest that cells must be in cycle or in a state of competence to be susceptible to CTL-induced apoptosis. Transformation of cells with c-myc enhanced their growth rate and rendered them very susceptible to CTLinduced apoptosis, but the specific role of c-myc in apoptosis is unclear. Our analyses by immunofluorescence of c-rayc protein levels between the targets shown in Figs. 3 and 4 did not reveal a corresponding relationship with their levels of DNA fragmentation. Since others have shown that antisense to c-myc can block antigen receptor-induced apoptosis in T cells (26) , we asked whether similar treatment of target cells would block CTL-induced apoptosis. Although a 4-18-h treatment of P815 and L929 cells with antisense to c-myc (5'-CACGTGAGGGGCAT-3') significantly reduced myc protein levels and arrested the cells in the Gt (but not Go) phase of the cell cycle, as shown previously (27), it did not impair the level of CTL-induced DNA fragmentation versus untreated targets (data not shown). This suggests that c-myr, per se, is only indirectly involved in rendering targets sensitive to CTL-induced apoptosis.