美国威斯康辛血液研究所Weiguo Cui小组的一项最新研究，揭示了CD4阳性T细胞的帮助是形成细胞溶解性CD8阳性T细胞亚群所必需的，从而保护机体免受慢性感染和癌症。这一研究成果2019年12月3日在线发表在国际学术期刊《免疫》上。

通过使用单细胞RNA测序，研究人员发现响应慢性感染的CD8阳性T细胞比以前意识到的异质性更高。重要的是，这些发现揭示了表达CX3CR1的CD8阳性T细胞亚群的形成，其表现出强大的溶细胞功能，是病毒控制所必需的。值得注意的是，这些数据进一步证明了这种细胞毒性亚群的形成严重依赖于白细胞介素21（IL-21）的CD4阳性T细胞帮助，并且该发育途径的开发可用于治疗性CD8阳性T细胞杀伤功能的肿瘤浸润增强。这些发现揭示了在持续感染过程中“ CD4阳性T细胞帮助”如何调节CD8阳性T细胞分化的其他分子机制，并且对优化免疫疗法中保护性CD8阳性T细胞的产生有影响。

据介绍，尽管CD4阳性T细胞的“帮助”对于维持抗病毒免疫至关重要，但在慢性感染过程中CD4阳性T细胞调节CD8阳性T细胞分化的机制仍然不清楚。

附：英文原文

Title: CD4+ T Cell Help Is Required for the Formation of a Cytolytic CD8+ T Cell Subset that Protects against Chronic Infection and Cancer

Author: Ryan Zander, David Schauder, Gang Xin, Christine Nguyen, Xiaopeng Wu, Allan Zajac, Weiguo Cui

Issue&Volume: December 03, 2019

Abstract: Although CD4+ T cell “help” is crucial to sustain antiviral immunity, the mechanisms by which CD4+ T cells regulate CD8+ T cell differentiation during chronic infection remain elusive. Here, using single-cellRNA sequencing, we show that CD8+ T cells responding to chronic infection were more heterogeneous than previously appreciated.Importantly, our findings uncovered the formation of a CX3CR1-expressing CD8+ T cell subset that exhibited potent cytolytic function and was required for viralcontrol. Notably, our data further demonstrate that formation of this cytotoxic subsetwas critically dependent on CD4+ T cell help via interleukin-21 (IL-21) and that exploitation of this developmentalpathway could be used therapeutically to enhance the killer function of CD8+ T cells infiltrated into the tumor. These findings uncover additional molecular mechanismsof how “CD4+ T cell help” regulates CD8+ T cell differentiation during persistent infection and have implications toward optimizingthe generation of protective CD8+ T cells in immunotherapy.

DOI: 10.1016/j.immuni.2019.10.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30453-4