CD8 memory precursor cell generation is a continuous process
Helena Todorov,
Margaux Prieux,
Daphne Laubreton,
Matteo Bouvier,
Shaoying Wang,
Simon de Bernard,
Christophe Arpin,
Robrecht Cannoodt,
Wouter Saelens,
Arnaud Bonnaffoux,
Olivier Gandrillon,
Fabien Crauste,
Yvan Saeys,
Jacqueline Marvel
Affiliations
Helena Todorov
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium
Margaux Prieux
Centre International de recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Superieure de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Laboratoire de Biologie et de Modélisation de la cellule, Université de Lyon, ENS de Lyon, CNRS UMR 5239, INSERM U1210, Lyon, France
Daphne Laubreton
Centre International de recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Superieure de Lyon, Université Claude Bernard Lyon 1, Lyon, France
Matteo Bouvier
Laboratoire de Biologie et de Modélisation de la cellule, Université de Lyon, ENS de Lyon, CNRS UMR 5239, INSERM U1210, Lyon, France; Vidium, Lyon, France
Shaoying Wang
Centre International de recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Superieure de Lyon, Université Claude Bernard Lyon 1, Lyon, France
Simon de Bernard
AltraBio, Lyon, France
Christophe Arpin
Centre International de recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Superieure de Lyon, Université Claude Bernard Lyon 1, Lyon, France
Robrecht Cannoodt
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium; Data Intuitive, Lebbeke, Belgium
Wouter Saelens
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium
Arnaud Bonnaffoux
Vidium, Lyon, France
Olivier Gandrillon
Laboratoire de Biologie et de Modélisation de la cellule, Université de Lyon, ENS de Lyon, CNRS UMR 5239, INSERM U1210, Lyon, France; Inria, Villeurbanne, France
Fabien Crauste
Laboratoire MAP5 (UMR CNRS 8145), Université de Paris, Paris, France
Yvan Saeys
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium
Jacqueline Marvel
Centre International de recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Superieure de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Corresponding author
Summary: In this work, we studied the generation of memory precursor cells following an acute infection by analyzing single-cell RNA-seq data that contained CD8 T cells collected during the postinfection expansion phase. We used different tools to reconstruct the developmental trajectory that CD8 T cells followed after activation. Cells that exhibited a memory precursor signature were identified and positioned on this trajectory. We found that these memory precursors are generated continuously with increasing numbers arising over time. Similarly, expression of genes associated with effector functions was also found to be raised in memory precursors at later time points. The ability of cells to enter quiescence and differentiate into memory cells was confirmed by BrdU pulse-chase experiment in vivo. Analysis of cell counts indicates that the vast majority of memory cells are generated at later time points from cells that have extensively divided.