Bullock M Elise, Hogan Thea, Williams Cayman, Morris Sinead, Nowicka Maria, Sharjeel Minahil, van Dorp Christiaan, Yates Andrew J, Seddon Benedict
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA.
Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, United Kingdom.
bioRxiv. 2024 Jun 25:2023.10.16.562650. doi: 10.1101/2023.10.16.562650.
Quantifying the kinetics with which memory T cell populations are generated and maintained is essential for identifying the determinants of the duration of immunity. The quality and persistence of circulating CD4 effector memory (T) and central memory (T) T cells in mice appear to shift with age, but it is unclear whether these changes are driven by the aging host environment, by cell age effects, or both. Here we address these issues by combining DNA labelling methods, established fate-mapping systems, a novel reporter mouse strain, and mathematical models. Together, these allow us to quantify the dynamics of both young and established circulating memory CD4 T cell subsets, within both young and old mice. We show that that these cells and their descendents become more persistent the longer they reside within the T and T pools. This behaviour may limit memory CD4 T cell diversity by skewing TCR repertoires towards clones generated early in life, but may also compensate for functional defects in new memory cells generated in old age.
量化记忆性T细胞群体产生和维持的动力学对于确定免疫持续时间的决定因素至关重要。小鼠循环CD4效应记忆（T）细胞和中枢记忆（T）细胞的质量和持久性似乎随年龄而变化，但尚不清楚这些变化是由衰老的宿主环境、细胞年龄效应还是两者共同驱动的。在这里，我们通过结合DNA标记方法、既定的命运图谱系统、一种新型报告小鼠品系和数学模型来解决这些问题。这些方法共同使我们能够量化年轻和年老小鼠体内年轻和已建立的循环记忆CD4 T细胞亚群的动态变化。我们表明，这些细胞及其后代在T和T池中停留的时间越长，就越持久。这种行为可能会通过使TCR库偏向生命早期产生的克隆来限制记忆性CD4 T细胞的多样性，但也可能补偿老年产生的新记忆细胞中的功能缺陷。
