Asymmetric cell division safeguards memory CD8 T cell development

The cellular microenvironment regulates CX3CR1 expression on CD8+ T cells and the maintenance of CX3CR1+ CD8+ T cells

“…Another possibility is that in vitro priming through CD3 and CD28, even in the presence of inflammatory stimuli is insufficient to drive CD8 + T-cell differentiation toward the development of the most highly differentiated T cells. This is consistent with a recent report showing that CD8 + T-cell priming by CD3 and CD28 antibodies is weaker than by dendritic cells presenting high-affinity peptides, and leads to biologically distinct responses [70,71]. It is also consistent with our observation that CD62L is only transiently downregulated upon priming through CD3 and CD28 stimulation, and only a few primed cells remain CD62Lthrough later divisions.…”

CD8 T‐cell diversification: Asymmetric cell division and its functional implications

“…Emerging new imaging and live cell manipulation technologies might further allow for analyses of ACD at higher resolution, such as a combined imaging and transcriptional analysis of asymmetrically divided sister cells, potentially revealing new fate‐determining targets [75, 76]. Inhibition and enforcement of ACD has been proven feasible for enhanced differentiation into a specific fate trajectory, emphasizing potential for clinical applications [32, 33, 61]. In summary, further research on ACD‐mediated fate diversification in CD8 T‐cells is necessary and the implementation of new single‐cell technologies will provide tools allowing to further expand our knowledge on the role, mechanistic functioning, and modulation of ACD.…”

“…The latter instead induces higher frequencies of memory precursor cells and lower ACD rates [41, 42, 46, 60]. We recently analyzed the interplay between ACD and TCR stimulation strength and their combined impact on subsequent fate acquisition of the progeny cells by using image‐based live single cell approaches [61]. Strikingly, ACD induced by high‐affinity ligand‐mediated activation of the TCR caused single cells to establish mixed‐fate colonies comprising both effector and memory precursor cells.…”

“…By inhibiting ACD only during the first mitosis versus additionally during all subsequent cell divisions, it was shown that it is likely the very first cell division after activation that drives fate divergence within the emerging progeny. Again, this was specifically attributed to strong TCR stimulation [61].…”

“…Of note, studies that show the latter have been performed upon strong TCR activation conditions. Preventing ACD by the inhibition of PKCζ during the first mitosis upon activation results in decreased memory potential, specifically upon strong TCR stimulation [61]. Whether PKCζ is only segregated asymmetrically upon strong TCR stimulation, possibly in order to mediate ACD, remains to be shown.…”