Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA; Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA, USA.
Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA; Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA, USA; Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN, US.
Cell Rep. 2021 Nov 9;37(6):109981. doi: 10.1016/j.celrep.2021.109981.
Memory T cells exhibit considerable diversity that determines their ability to be protective. Here, we examine whether changes in T cell heterogeneity contribute to the age-associated failure of immune memory. By screening for age-dependent T cell-surface markers, we identify CD4 and CD8 memory T cell subsets that are unrelated to previously defined subsets of central and effector memory cells. Memory T cells expressing the ecto-5'-nucleotidase CD73 constitute a functionally distinct subset of memory T cells that declines with age. They resemble long-lived, polyfunctional memory cells but are also poised to display effector functions and to develop into cells resembling tissue-resident memory T cells (T). Upstream regulators of differential chromatin accessibility and transcriptomes include transcription factors that facilitate CD73 expression and regulate TRM differentiation. CD73 is not just a surrogate marker of these regulatory networks but is directly involved in T cell survival.
记忆 T 细胞表现出相当大的多样性，这种多样性决定了它们的保护能力。在这里，我们研究了 T 细胞异质性的变化是否导致与年龄相关的免疫记忆失败。通过筛选与年龄相关的 T 细胞表面标志物，我们鉴定出与先前定义的中央记忆细胞和效应记忆细胞无关的 CD4 和 CD8 记忆 T 细胞亚群。表达外核苷酸酶 CD73 的记忆 T 细胞构成了记忆 T 细胞的一个功能不同的亚群，随着年龄的增长而减少。它们类似于长寿、多功能的记忆细胞，但也准备好表现出效应功能，并发展成类似于组织驻留记忆 T 细胞 (T) 的细胞。差异染色质可及性和转录组的上游调节因子包括促进 CD73 表达和调节 TRM 分化的转录因子。CD73 不仅仅是这些调节网络的替代标志物，而是直接参与 T 细胞的存活。
