Real-time tracking of cell cycle progression during CD8(+) effector and memory T-cell differentiation
- Author(s)
- Kinjyo, I; Qin, J; Tan, SY; Wellard, CJ; Mrass, P; Ritchie, W; Doi, A; Cavanagh, LL; Tomura, M; Sakaue-Sawano, A; Kanagawa, O; Miyawaki, A; Hodgkin, PD; Weninger, W;
- Journal Title
- Nat Commun
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NPG
- Research Division(s)
- Immunology
- Publisher's Version
- https://doi.org/10.1038/ncomms7301
- Open Access at Publisher's Site
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Creation Date: 2015-02-26 11:26:53
Last Modified: 2015-05-12 09:41:04