Department of Biological Sciences, University of California, San Diego, La Jolla, CA.
Department of Biological Sciences, University of California, San Diego, La Jolla, CA
J Exp Med. 2018 Mar 5;215(3):773-783. doi: 10.1084/jem.20171584. Epub 2018 Feb 12.
CD8 T cells responding to infection differentiate into a heterogeneous population composed of progeny that are short-lived and participate in the immediate, acute response and those that provide long-lasting host protection. Although it is appreciated that distinct functional and phenotypic CD8 T cell subsets persist, it is unclear whether there is plasticity among subsets and what mechanisms maintain subset-specific differences. Here, we show that continued Id2 regulation of E-protein activity is required to maintain the KLRG1 CD8 T cell population after lymphocytic choriomeningitis virus infection. Induced deletion of phenotypically and transcriptionally transformed the KLRG1 "terminal" effector/effector-memory CD8 T cell population into a KLRG1 memory-like population, promoting a gene-expression program that resembled that of central memory T cells. Our results question the idea that KLRG1 CD8 T cells are necessarily terminally programmed and suggest that sustained regulation is required to maintain distinct CD8 T cell states.
CD8 T 细胞对感染的反应会分化成一个异质群体，由寿命较短的、参与即时急性反应的祖细胞和提供长期宿主保护的祖细胞组成。尽管人们已经认识到不同功能和表型的 CD8 T 细胞亚群持续存在，但尚不清楚亚群之间是否存在可塑性，以及哪些机制维持亚群特异性差异。在这里，我们表明，在淋巴细胞性脉络丛脑膜炎病毒感染后，持续的 Id2 调节 E 蛋白活性对于维持 KLRG1 CD8 T 细胞群体是必需的。表型和转录诱导的删除将 KLRG1“终末”效应器/效应器记忆 CD8 T 细胞群体转化为 KLRG1 记忆样群体，促进类似于中央记忆 T 细胞的基因表达程序。我们的结果质疑了 KLRG1 CD8 T 细胞必然是终末程序化的观点，并表明需要持续的调节来维持不同的 CD8 T 细胞状态。
