A Single-Cell Perspective on Memory T-Cell Differentiation

Memory differentiation of CD4 and CD8 T-cell populations has been extensively studied and many key molecular players and transcriptional networks have been identified. But how regulatory principles, identified on this population level, translate to immune responses that originate fromsingle antigen-specific T cells is only nowbeing elucidated. Here, we provide a short summary of the approaches used for mapping the fate of individual T cells and their progeny in vivo. We then highlight which major questions, with respect to memory T-cell differentiation, have been addressed by studying the development of single-cell-derived T-cell families during infection or vaccination. We discuss how fate decisions of single T cells are modulated by the affinity of their TCR and further shaped through a coregulation of T-cell differentiation and T-cell proliferation. These current findings indicate the early segregation into slowly dividing T central memory precursors (CMPs) and rapidly dividing non-CMPs, as a key event that separates the developmental paths of long- and short-lived T cells.

Automated summary

This study focuses on the memory differentiation of CD4 and CD8 T-cell populations, and how regulatory principles identified on a population level translate to immune responses originating from single antigen-specific T cells. It explores the fate decisions of single T cells modulated by TCR affinity and coregulation of T-cell differentiation and proliferation, with findings indicating a key event of early segregation into distinct T central memory precursors.