Real-time tracking of cell cycle progression during CD8(+) effector and memory T-cell differentiation
Web of Science
AuthorKinjyo, I; Qin, J; Tan, S-Y; Wellard, CJ; Mrass, P; Ritchie, W; Doi, A; Cavanagh, LL; Tomura, M; Sakaue-Sawano, A; ...
Source TitleNature Communications
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sHodgkin, Philip
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsKinjyo, I., Qin, J., Tan, S. -Y., Wellard, C. J., Mrass, P., Ritchie, W., Doi, A., Cavanagh, L. L., Tomura, M., Sakaue-Sawano, A., Kanagawa, O., Miyawaki, A., Hodgkin, P. D. & Weninger, W. (2015). Real-time tracking of cell cycle progression during CD8(+) effector and memory T-cell differentiation. NATURE COMMUNICATIONS, 6 (1), https://doi.org/10.1038/ncomms7301.
Access StatusOpen Access
The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.
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