Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection

Ran He; Shiyue Hou; Cheng Liu; Anli Zhang; Qiang Bai; Miao Han; Yu Yang; Gang Wei; Ting Shen; Xinxin Yang; Lifan Xu; Xiangyu Chen; Yaxing Hao; Pengcheng Wang; Chuhong Zhu; Juanjuan Ou; Houjie Liang; Ting Ni; Xiaoyan Zhang; Xinyuan Zhou; Kai Deng; Yaokai Chen; Yadong Luo; Jianqing Xu; Hai Qi; Yuzhang Wu; Lilin Ye

doi:10.1038/nature19317

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Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection

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Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection

Ran He, Shiyue Hou, Cheng Liu, Anli Zhang, Qiang Bai, Miao Han, Yu Yang, Gang Wei, Ting Shen, Xinxin Yang, …

Nature (London), Vol.537(7620), pp.412-416

15/09/2016

DOI: https://doi.org/10.1038/nature19317

PMID: 27501245

Résumé

Adoptive Transfer

Animals

B-Lymphocytes - immunology

Basic Helix-Loop-Helix Transcription Factors - metabolism

CD8-Positive T-Lymphocytes - cytology

CD8-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - metabolism

CD8-Positive T-Lymphocytes - transplantation

Cell Differentiation

Chronic Disease

Female

Germinal Center - cytology

Germinal Center - immunology

HIV Infections - immunology

HIV Infections - virology

Humans

Inhibitor of Differentiation Protein 2 - metabolism

Lymphocytic Choriomeningitis - immunology

Lymphocytic Choriomeningitis - virology

Lymphocytic choriomeningitis virus - growth & development

Lymphocytic choriomeningitis virus - immunology

Male

Mice

Receptors, CXCR5 - deficiency

Receptors, CXCR5 - metabolism

Signal Transduction

T-Lymphocyte Subsets - cytology

T-Lymphocyte Subsets - immunology

T-Lymphocyte Subsets - metabolism

T-Lymphocyte Subsets - transplantation

Viral Load - immunology

Virus Replication - immunology

During chronic viral infection, virus-specific CD8(+) T cells become exhausted, exhibit poor effector function and lose memory potential. However, exhausted CD8(+) T cells can still contain viral replication in chronic infections, although the mechanism of this containment is largely unknown. Here we show that a subset of exhausted CD8(+) T cells expressing the chemokine receptor CXCR5 has a critical role in the control of viral replication in mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). These CXCR5(+) CD8(+) T cells were able to migrate into B-cell follicles, expressed lower levels of inhibitory receptors and exhibited more potent cytotoxicity than the CXCR5(-) [corrected] subset. Furthermore, we identified the Id2-E2A signalling axis as an important regulator of the generation of this subset. In patients with HIV, we also identified a virus-specific CXCR5(+) CD8(+) T-cell subset, and its number was inversely correlated with viral load. The CXCR5(+) subset showed greater therapeutic potential than the CXCR5(-) [corrected] subset when adoptively transferred to chronically infected mice, and exhibited synergistic reduction of viral load when combined with anti-PD-L1 treatment. This study defines a unique subset of exhausted CD8(+) T cells that has a pivotal role in the control of viral replication during chronic viral infection.

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Détails

Titre: Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection
Créateurs - sans rôle: Ran He - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Shiyue Hou - Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, Beijing 100084, China
Cheng Liu - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Anli Zhang - Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China
Qiang Bai - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Miao Han - State Key Laboratory of Genetic Engineering &MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China
Yu Yang - Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China
Gang Wei - State Key Laboratory of Genetic Engineering &MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China
Ting Shen - State Key Laboratory of Genetic Engineering &MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China
Xinxin Yang - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Lifan Xu - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Xiangyu Chen - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Yaxing Hao - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Pengcheng Wang - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Chuhong Zhu - Department of Anatomy, School of Basic Medicine, Third Military Medical University, Chongqing 400038, China
Juanjuan Ou - Department of Oncology, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China
Houjie Liang - Department of Oncology, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China
Ting Ni - State Key Laboratory of Genetic Engineering &MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China
Xiaoyan Zhang - Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China
Xinyuan Zhou - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Kai Deng - Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Yaokai Chen - Chongqing Public Health Medical Center, Chongqing 400000, China
Yadong Luo - Chongqing Public Health Medical Center, Chongqing 400000, China
Jianqing Xu - Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China
Hai Qi - Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, Beijing 100084, China
Yuzhang Wu - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Lilin Ye - Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Détails de publication: Nature (London), Vol.537(7620), pp.412-416
Identifiants: 99148704309311
Unité académique: Physiologie et Médecine Expérimentale du coeur et des muscles - PhyMedExp
Langue: English
Type de ressource: Journal article