美国埃默里大学医学院Rafi Ahmed研究团队近期工作揭示，在慢性感染过程中，PD-1⁺干细胞样CD8⁺T细胞可出现具有效应样转录特征的暂时性T细胞的增殖。相关论文2019年12月3日在线发表于国际学术期刊《免疫》。

研究人员表示，T细胞功能障碍是慢性病毒感染和癌症的特征。慢性淋巴细胞性脑膜炎病毒（LCMV）感染的最新研究已定义了PD-1⁺Tcf-1⁺CD8⁺T细胞亚群，能够自我更新并分化为下调Tcf-1并表达其他抑制性分子（如Tim3）的终末分化细胞。

研究人员证明糖蛋白CD101的表达将这种终末分化的种群分为两个亚群。干细胞样Tcf-1⁺CD8⁺T细胞最初分化为CD101^-Tim3⁺细胞的短暂类群，随后转变为CD101⁺Tim3⁺细胞。最近产生的CD101^-Tim3⁺细胞在体内增殖，有助于病毒控制，并具有类似趋化因子受体CX3CR1、促炎性细胞因子和颗粒酶B的效应子样转录特征。PD-1途径阻断增加了CD101^-Tim3⁺CD8⁺T细胞分化的数量，表明这些新生成的过渡细胞在PD-1免疫治疗中起着关键作用。

附：英文原文

Title: Proliferating Transitory T Cells with an Effector-like Transcriptional Signature Emerge from PD-1+ Stem-like CD8+ T Cells during Chronic Infection

Author: William H. Hudson, Julia Gensheimer, Masao Hashimoto, Andreas Wieland, Rajesh M. Valanparambil, Peng Li, Jian-Xin Lin, Bogumila T. Konieczny, Se Jin Im, Gordon J. Freeman, Warren J. Leonard, Haydn T. Kissick, Rafi Ahmed

Issue&Volume: December 03, 2019

Abstract: T cell dysfunction is a characteristic feature of chronic viral infection and cancer.Recent studies in chronic lymphocytic choriomeningitis virus (LCMV) infection havedefined a PD-1+ Tcf-1+ CD8+ T cell subset capable of self-renewal and differentiation into more terminally differentiatedcells that downregulate Tcf-1 and express additional inhibitory molecules such asTim3. Here, we demonstrated that expression of the glycoprotein CD101 divides thisterminally differentiated population into two subsets. Stem-like Tcf-1+ CD8+ T cells initially differentiated into a transitory population of CD101Tim3+ cells that later converted into CD101+ Tim3+ cells. Recently generated CD101Tim3+ cells proliferated in vivo, contributed to viral control, and were marked by an effector-like transcriptionalsignature including expression of the chemokine receptor CX3CR1, pro-inflammatorycytokines, and granzyme B. PD-1 pathway blockade increased the numbers of CD101Tim3+ CD8+ T cells, suggesting that these newly generated transitional cells play a criticalrole in PD-1-based immunotherapy.

DOI: 10.1016/j.immuni.2019.11.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30460-1