Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
JetBrains Research, Paphos 8021, Cyprus.
Immunity. 2024 Oct 8;57(10):2362-2379.e10. doi: 10.1016/j.immuni.2024.08.019. Epub 2024 Sep 24.
Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38 expression universally identified CD8 and CD4 RTEs. We further determined the dynamics of RTEs and mature cells in a cohort of 158 individuals, including age-associated transcriptional reprogramming and shifts in cytokine production. Spectral cytometry profiling revealed two axes of aging common to naive CD8 and CD4 T cells: (1) a decrease in CD38 cells (RTEs) and (2) an increase in CXCR3 cells. Identification of RTEs enables direct assessment of thymic health. Furthermore, resolving the dynamics of naive T cell remodeling yields insight into vaccination and infection responsiveness throughout aging.
胸腺萎缩是人类免疫衰老的一个关键因素，导致胸腺输出减少，循环中近期产生的胸腺迁出细胞（RTE）幼稚 T 细胞减少。目前，人类 RTE 及其相应的细胞表面标志物的确切定义尚不清楚。通过对单细胞 RNA-seq/ATAC-seq 数据的分析，SOX4、IKZF2 和 TOX 以及 CD38 蛋白的表达将 RTEs 区分开来，其中表面 CD38 表达普遍识别 CD8 和 CD4 RTEs。我们进一步在包括年龄相关转录重编程和细胞因子产生变化的 158 个人群队列中确定了 RTEs 和成熟细胞的动态。光谱细胞术分析揭示了两个与幼稚 CD8 和 CD4 T 细胞衰老相关的共同轴：（1）CD38 细胞（RTEs）减少，（2）CXCR3 细胞增加。RTE 的鉴定可以直接评估胸腺健康。此外，解析幼稚 T 细胞重塑的动态可以深入了解整个衰老过程中的疫苗接种和感染反应。
