Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation Academic Article uri icon

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.

authors

  • Kinjyo, Ichiko
  • Qin, Jim
  • Tan, Sioh-Yang
  • Wellard, Cameron J
  • Mrass, Paulus
  • Ritchie, William
  • Doi, Atsushi
  • Cavanagh, Lois L
  • Tomura, Michio
  • Sakaue-Sawano, Asako
  • Kanagawa, Osami
  • Miyawaki, Atsushi
  • Hodgkin, Philip D
  • Weninger, Wolfgang

publication date

  • 2015