White Jason T, Cross Eric W, Burchill Matthew A, Danhorn Thomas, McCarter Martin D, Rosen Hugo R, O'Connor Brian, Kedl Ross M
Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, School of Medicine, Aurora, Colorado 80045, USA.
Department of Medicine and Division of Gastroenterology and Hepatology, University of Colorado Denver at Anschutz Medical Campus, School of Medicine, Aurora, Colorado 80045, USA.
Nat Commun. 2016 Apr 21;7:11291. doi: 10.1038/ncomms11291.
Virtual memory cells (VM) are an antigen-specific, memory phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM cells were the result of homeostatic proliferation (HP) resembling the proliferation observed in a lymphopenic environment. Here we demonstrate that HP is ongoing in lymphoreplete mice, the degree of which is dictated by the number of naive CD8 T cells with a sufficiently high affinity for self-antigen interacting with peripheral IL-15. VM cell transcriptional profiles suggest a capacity to mediate protective immunity via antigen non-specific bystander killing, a function we show is dependent on IL-15. Finally, we show a VM-like population of human cells that accumulate with age and traffic to the liver, displaying phenotypic and functional attributes consistent with the bystander protective functions of VM cells identified in the mouse. These data identify developmental and functional attributes of VM cells, including their likely role in protective immunity.
虚拟记忆细胞（VM）是在淋巴细胞充足、未受刺激的小鼠中发现的一种抗原特异性、记忆表型的CD8 T细胞亚群。先前的研究表明，VM细胞是稳态增殖（HP）的结果，类似于在淋巴细胞减少环境中观察到的增殖。在这里，我们证明HP在淋巴细胞充足的小鼠中持续存在，其程度由对与外周IL-15相互作用的自身抗原有足够高亲和力的初始CD8 T细胞数量决定。VM细胞转录谱表明其具有通过抗原非特异性旁观者杀伤介导保护性免疫的能力，我们证明这一功能依赖于IL-15。最后，我们发现了一群类似VM的人类细胞，它们随着年龄增长而积累并迁移至肝脏，表现出与在小鼠中鉴定出的VM细胞旁观者保护功能一致的表型和功能特性。这些数据确定了VM细胞的发育和功能特性，包括它们在保护性免疫中可能发挥的作用。
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