虚拟内存CD8⁺ 衰老中的T细胞：异质性、旁观者保护、炎症潜能和抑制性调节

摘要(中文译文)

衰老通过初始细胞库的收缩和记忆表型群体的扩增重塑CD8⁺ T细胞区室，其中包括抗原未经历型虚拟记忆（virtual memory，VM）CD8⁺ T细胞的进行性积累。VM CD8⁺ T细胞在缺乏外源抗原致敏的情况下产生，并获得类记忆表型。在衰老宿主中，VM CD8⁺ T细胞构成抗原未经历型记忆表型CD8⁺ T细胞库的相当大一部分，其分化受自身反应性、稳态细胞因子以及与IL-15和EOMES相关的转录程序所塑造。在衰老过程中，VM CD8⁺ T细胞数量积累，表现出改变的增殖反应，保留对稳态和炎症细胞因子的敏感性，并可在感染期间维持效应功能。这些特征提示，VM CD8⁺ T细胞可能通过提供快速的类效应反应，部分代偿与年龄相关的初始CD8⁺ T细胞丢失。与此同时，衰老的VM CD8⁺ T细胞似乎由异质性亚群组成，包括具有细胞毒性和炎症潜能的群体。新出现的证据提示，抑制性受体可能在衰老过程中标记不同的VM状态，尽管其功能意义和潜在的调控作用仍有待确立。

Abstract

Aging reshapes the CD8⁺ T cell compartment through contraction of the naïve pool and expansion of memory-phenotype populations, including the progressive accumulation of antigen-inexperienced virtual memory (VM) CD8⁺ T cells. VM CD8⁺ T cells arise in the absence of foreign antigen priming and acquire a memory-like phenotype. In aged hosts, VM CD8⁺ T cells constitute a substantial fraction of the antigen-inexperienced memory-phenotype CD8⁺ T cell pool, and their differentiation is shaped by self-reactivity, homeostatic cytokines, and transcriptional programs linked to IL-15 and EOMES. During aging, VM CD8⁺ T cells accumulate numerically, display altered proliferative responses, retain sensitivity to homeostatic and inflammatory cytokines, and can preserve effector function during infection. These features suggest that VM CD8⁺ T cells may partially compensate for the age-associated loss of naïve CD8⁺ T cells by providing rapid effector-like responses. At the same time, aged VM CD8⁺ T cells appear to comprise heterogeneous subsets, including populations with cytotoxic and inflammatory potential. Emerging evidence suggests that inhibitory receptors may mark distinct VM states during aging, although their functional significance and potential regulatory role remain to be established.

如何引用

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