State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangzhou National Laboratory, Bioland, Guangzhou, Guangdong, China.
Front Immunol. 2024 Jan 9;14:1334597. doi: 10.3389/fimmu.2023.1334597. eCollection 2023.
Memory T (Tm) cells are a subpopulation of immune cells with great heterogeneity. Part of this diversity came from T cells that were primed with different viruses. Understanding the differences among different viral-specific Tms will help develop new therapeutic strategies for viral infections.
In this study, we compared the transcriptome of Tm cells that primed with CMV, EBV and SARS-CoV-2 with single-cell sequencing and studied the similarities and differences in terms of subpopulation composition, activation, metabolism and transcriptional regulation.
We found that CMV is marked by plentiful cytotoxic Temra cells, while EBV is more abundant in functional Tem cells. More importantly, we found that CD28 and CTLA4 can be used as continuous indicators to interrogate the antiviral ability of T cells. Furthermore, we proposed that REL is a main regulatory factor for CMV-specific T cells producing cytokines and plays an antiviral role.
Our data gives deep insight into molecular characteristics of Tm subsets from different viral infection, which is important to understand T cell immunization. Furthermore, our results provide basic background knowledges for T cell based vaccine development in future.
记忆 T(Tm)细胞是具有高度异质性的免疫细胞亚群。这种多样性的一部分来自于被不同病毒引发的 T 细胞。了解不同病毒特异性 Tm 细胞之间的差异将有助于为病毒感染开发新的治疗策略。
在这项研究中,我们通过单细胞测序比较了被 CMV、EBV 和 SARS-CoV-2 引发的 Tm 细胞的转录组,并研究了在亚群组成、激活、代谢和转录调控方面的相似性和差异。
我们发现 CMV 以大量细胞毒性 Temra 细胞为特征,而 EBV 则在功能 Tem 细胞中更为丰富。更重要的是,我们发现 CD28 和 CTLA4 可以作为连续指标来检测 T 细胞的抗病毒能力。此外,我们提出 REL 是 CMV 特异性 T 细胞产生细胞因子的主要调节因子,发挥抗病毒作用。
我们的数据深入了解了来自不同病毒感染的 Tm 细胞亚群的分子特征,这对于理解 T 细胞免疫很重要。此外,我们的结果为未来基于 T 细胞的疫苗开发提供了基本的背景知识。