The stage at which memory CD8 T cells diverge after a viral infection remains debated. These cells are essential for effective protection of individuals during subsequent infection. Identification of the stage at which they are generated may impact strategic choices in modulating their generation in a therapeutic aim. The results published in the journal iScience allow to reconstruct their trajectory from single cell transcriptomic data using machine learning tools.

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.

Reference: CD8 memory precursor cell generation is a continuous process. Todorov H, Prieux M, Laubreton D, Bouvier M, Wang S, de Bernard S, Arpin C, Cannoodt R, Saelens W, Bonnaffoux A, Gandrillon O, Crauste F, Saeys Y, Marvel J. iScience., September 16, 2022.
DOI: 10.1016/j.isci.2022.104927