Virus infection pattern imprinted and diversified the differentiation of T-cell memory in transcription and function

Yuan Wang; Xinyue Mei; Zhengfang Lin; Xiaoyun Yang; Jinpeng Cao; Jiaying Zhong; Junxiang Wang; Li Cheng; Zhongfang Wang

doi:10.3389/fimmu.2023.1334597

Virus infection pattern imprinted and diversified the differentiation of T-cell memory in transcription and function

Front Immunol. 2024 Jan 9:14:1334597. doi: 10.3389/fimmu.2023.1334597. eCollection 2023.

Authors

Yuan Wang^#^{1

2}, Xinyue Mei^#¹, Zhengfang Lin¹, Xiaoyun Yang^{1

2}, Jinpeng Cao^{1

2}, Jiaying Zhong¹, Junxiang Wang¹, Li Cheng¹, Zhongfang Wang^{1

2}

Affiliations

¹ 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.
² Guangzhou National Laboratory, Bioland, Guangzhou, Guangdong, China.

^# Contributed equally.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: CMV; EBV - Epstein-Barr virus; SARS-C0V-2; T cell differentiation; memory T cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents
Cell Differentiation
Cytomegalovirus Infections*
Humans
Memory T Cells
Virus Diseases*

Substances

Antiviral Agents

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Key R&D Program of China (2019YFC0810900, 2022YFC2604104), Sponsored by the grant of State Key Laboratory of Respiratory Disease (SKLRD-Z-202 321), S&T Program of Guangzhou Laboratory (SRPG22-006), the National Natural Science Foundation of China (81971485, 82271801), Guangdong Basic and Applied Basic Research Foundation (2019B1515120068, 2020B11113300, 2022B1111070002, 2019A1515110782), and Emergency Key Program of Guangzhou Laboratory (EKPG21-30-1).