Stochastic asymmetric repartition of lytic machinery in dividing CD8+ T cells generates heterogeneous killing behavior

Autor: Fanny Lafouresse, Romain Jugele, Sabina Müller, Marine Doineau, Valérie Duplan-Eche, Eric Espinosa, Marie-Pierre Puisségur, Sébastien Gadat, Salvatore Valitutti
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: eLife, Vol 10 (2021)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.62691
Popis: 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.
Databáze: Directory of Open Access Journals