Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
Medical Sciences Division, NDORMS, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Nat Commun. 2021 May 11;12(1):2715. doi: 10.1038/s41467-021-22954-y.
Efficient immune responses rely on heterogeneity, which in CD8 T cells, amongst other mechanisms, is achieved by asymmetric cell division (ACD). Here we find that ageing, known to negatively impact immune responses, impairs ACD in murine CD8 T cells, and that this phenotype can be rescued by transient mTOR inhibition. Increased ACD rates in mitotic cells from aged mice restore the expansion and memory potential of their cellular progenies. Further characterization of the composition of CD8 T cells reveals that virtual memory cells (T cells), which accumulate during ageing, have a unique proliferation and metabolic profile, and retain their ability to divide asymmetrically, which correlates with increased memory potential. The opposite is observed for naive CD8 T cells from aged mice. Our data provide evidence on how ACD modulation contributes to long-term survival and function of T cells during ageing, offering new insights into how the immune system adapts to ageing.
高效的免疫反应依赖于异质性，在 CD8 T 细胞中，除其他机制外，通过不对称细胞分裂（ACD）实现。在这里，我们发现已知会对免疫反应产生负面影响的衰老会损害小鼠 CD8 T 细胞中的 ACD，并且这种表型可以通过短暂的 mTOR 抑制来挽救。来自衰老小鼠的有丝分裂细胞中 ACD 率的增加恢复了其细胞后代的扩增和记忆潜能。对 CD8 T 细胞组成的进一步表征表明，在衰老过程中积累的虚拟记忆细胞（T 细胞）具有独特的增殖和代谢特征，并保留其不对称分裂的能力，这与增强的记忆潜能相关。从衰老小鼠中分离出的幼稚 CD8 T 细胞则相反。我们的数据提供了关于 ACD 调节如何有助于 T 细胞在衰老过程中的长期存活和功能的证据，为免疫系统如何适应衰老提供了新的见解。
