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 (C TL)-mediated apoptosis of LDb fibroblast target cells at different phases o f the cell cycle. When aphidicolin-synchronized target cells were exposed t o the CTL clone F5, apoptosis occurred with similar morphology during G1, S /G2 and M phase, showing that apoptosis and mitosis are not mutually exclus ive cellular events. Interestingly, following normal mitosis of target cell s that had been previously contacted by CTL, pairs of daughter cells would occasionally undergo apoptosis within minutes of each other. Such synchrono us post-mitotic apoptosis was also observed when using mitotically unsynchr onized target cells, and also when using d11S T cell hybridomas as alternat ive Fas- (CD95-) based effector cells, even if these effecters were physica lly washed away after an initial period of co-incubation with the target ce lls. Our observations show that cytotoxic cells can induce a condemned stat e in pre-mitotic target cells, which can be inherited by both daughter cell s, leading to their synchronous apoptosis after mitosis.