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 from single antigen-specific T cells is only now being 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.

中文翻译：

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记忆 T 细胞分化的单细胞视角

CD4 和 CD8 T 细胞群的记忆分化已被广泛研究，并且许多关键分子参与者和转录网络已被识别。但在这个群体水平上确定的调控原则如何转化为源自单一抗原特异性 T 细胞的免疫反应，现在才被阐明。在这里，我们提供了用于绘制个体 T 细胞及其后代体内命运的方法的简短总结。然后，我们强调通过研究感染或疫苗接种过程中单细胞衍生的 T 细胞家族的发育，已经解决了与记忆 T 细胞分化相关的主要问题。我们讨论了单个 T 细胞的命运决定如何通过其 TCR 的亲和力进行调节，并通过 T 细胞分化和 T 细胞增殖的共同调节进一步形成。目前的这些发现表明，早期分离为缓慢分裂的 T 中央记忆前体 (CMP) 和快速分裂的非 CMP，是区分长寿命和短寿命 T 细胞发育路径的关键事件。