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

中文翻译：

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在慢性感染过程中，PD-1 +茎状CD8 + T细胞出现具有效应子状转录特征的增殖性T细胞。

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细胞亚型，能够自我更新和分化为下调Tcf-1并表达其他抑制性分子的终末分化细胞。提姆3。在这里，我们证明了糖蛋白CD101的表达将这种终末分化的种群分为两个子集。茎状Tcf-1 + CD8 + T细胞最初分化为CD101-Tim3 +细胞的短暂种群，之后又转变为CD101 + Tim3 +细胞。最近产生的CD101-Tim3 +细胞在体内增殖，有助于控制病毒，