TY - JOUR TI - Stochastic asymmetric repartition of lytic machinery in dividing CD8+ T cells generates heterogeneous killing behavior AU - Lafouresse, Fanny AU - Jugele, Romain AU - Müller, Sabina AU - Doineau, Marine AU - Duplan-Eche, Valérie AU - Espinosa, Eric AU - Puisségur, Marie-Pierre AU - Gadat, Sébastien AU - Valitutti, Salvatore A2 - Robey, Ellen A A2 - Taniguchi, Tadatsugu VL - 10 PY - 2021 DA - 2021/01/11 SP - e62691 C1 - eLife 2021;10:e62691 DO - 10.7554/eLife.62691 UR - https://doi.org/10.7554/eLife.62691 AB - Cytotoxic immune cells are endowed with a high degree of heterogeneity in their lytic function, but how this heterogeneity is generated is still an open question. We therefore investigated if human CD8+ T cells could segregate their lytic components during telophase, using imaging flow cytometry, confocal microscopy, and live-cell imaging. We show that CD107a+-intracellular vesicles, perforin, and granzyme B unevenly segregate in a constant fraction of telophasic cells during each division round. Mathematical modeling posits that unequal lytic molecule inheritance by daughter cells results from the random distribution of lytic granules on the two sides of the cleavage furrow. Finally, we establish that the level of lytic compartment in individual cytotoxic T lymphocyte (CTL) dictates CTL killing capacity. KW - human lymphocytes KW - cytotoxic t lymphocytes KW - lytic granules KW - cell division KW - lysosomal-associated membrane proteins JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -