Themis suppresses the effector function of CD8+ T cells in acute viral infection

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外文摘要：CD8+ T cells play a central role in antiviral immune responses.Upon infection,naive CD8+ T cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved.Although extensively investigated,the underlying mechanisms of CD8+ T-cell differentiation remain incompletely understood.Themis is a T-cell-specific protein that plays critical roles in T-cell development.Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8+ T-cell homeostasis,cytokine responsiveness,and antibacterial responses.In this study,we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection.We found that preexisting CD8+ T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice.Further analyses showed that in the primary immune response,Themis deficiency promoted the differentiation of CD8+ effector cells and increased their TNF and IFNγ production.Moreover,Themis deficiency impaired memory precursor cell(MPEC)differentiation but promoted short-lived effector cell(SLEC)differentiation.Themis deficiency also enhanced effector cytokine production in memory CD8+ T cells while impairing central memory CD8+ T-cell formation.Mechanistically,we found that Themis mediates PD-1 expression and its signaling in effector CD8+ T cells,which explains the elevated cytokine production in these cells when Themis is disrupted.

外文关键词：

ThemisEffector T cellCD8 T-cell differentiationCytokineLCMV

作者：

Jian Tang、Xian Jia、Jian Li、Junchen Dong、Jiayu Wang、Wanyun Li、Yuzhen Zhu、Yanyan Hu、Bowen Hou、Chunjie Lin、Yu Cong、Tong Ren、Changsheng Yan、Hongying Yang、Qian Lai、Haiping Zheng、Yuzhou Bao、Namrata Gautam、Hong-Rui Wang、Bing Xu、Xiao Lei Chen、Qing Li、Nicholas R.J.Gascoigne、Guo Fu

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作者单位：

State Key Laboratory of Cellular Stress Biology,School of Medicine,Faculty of Medicine and Life Sciences,Xiamen University,Xiamen,China

School of Life Sciences,Xiamen University,Xiamen,China

Immunology Translational Research Programme,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,Singapore

Department of Microbiology and Immunology,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,Singapore

Department of Hematology,The First Affiliated Hospital and Institute of Hematology,School of Medicine,Xiamen University,Xiamen,China

Cancer Research Center of Xiamen University,Xiamen,China

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基金：

National Natural Science Foundation of ChinaFundamental Research Funds for the Central UniversitiesSingapore Ministry of EducationSingapore Ministry of Health's National Medical Research CouncilNatural Science Foundation of Fujian ProvinceNational Natural Science Foundation of China

项目编号：

3207088720720220003MOE-000112MOH-0005232019J01009U1904206

出版年：

2023

DOI：

10.1038/s41423-023-00997-z

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(5)

参考文献量51