Cytotoxic T lymphocytes can induce a condemned state and synchronous post-mitotic apoptosis of daughter target cells

We have used time-lapse video microscopy to study cytotoxic T lymphocyte (CTL)-mediated apoptosis of LDb fibroblast target cells at different phases of the cell cycle. When aphidicolin-synchronized target cells were exposed to the CTL clone F5, apoptosis occurred with similar morphology during G1, S/G2 and M phase, showing that apoptosis and mitosis are not mutually exclusive cellular events. Interestingly, following normal mitosis of target cells that had been previously contacted by CTL, pairs of daughter cells would occasionally undergo apoptosis within minutes of each other. Such synchronous post-mitotic apoptosis was also observed when using mitotically unsynchronized target cells, and also when using d11S T cell hybridomas as alternative Fas- (CD95-) based effector cells, even if these effectors were physically washed away after an initial period of co-incubation with the target cells. Our observations show that cytotoxic cells can induce a condemned state in pre-mitotic target cells, which can be inherited by both daughter cells, leading to their synchronous apoptosis after mitosis.