title: Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection.
abstract: 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.
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Ran
authors: R
authors: He
authors: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Shiyue
authors: S
authors: Hou
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Cheng
authors: C
authors: Liu
authors: Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
authors: Anli
authors: A
authors: Zhang
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Qiang
authors: Q
authors: Bai
authors: 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.
authors: Miao
authors: M
authors: Han
authors: Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
authors: Yu
authors: Y
authors: Yang
authors: 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.
authors: Gang
authors: G
authors: Wei
authors: 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.
authors: Ting
authors: T
authors: Shen
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Xinxin
authors: X
authors: Yang
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Lifan
authors: L
authors: Xu
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Xiangyu
authors: X
authors: Chen
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Yaxing
authors: Y
authors: Hao
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Pengcheng
authors: P
authors: Wang
authors: Department of Anatomy, School of Basic Medicine, Third Military Medical University, Chongqing 400038, China.
authors: Chuhong
authors: C
authors: Zhu
authors: Department of Oncology, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Juanjuan
authors: J
authors: Ou
authors: Department of Oncology, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Houjie
authors: H
authors: Liang
authors: 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.
authors: Ting
authors: T
authors: Ni
authors: Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
authors: Xiaoyan
authors: X
authors: Zhang
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Xinyuan
authors: X
authors: Zhou
authors: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors: Kai
authors: K
authors: Deng
authors: Chongqing Public Health Medical Center, Chongqing 400000, China.
authors: Yaokai
authors: Y
authors: Chen
authors: Chongqing Public Health Medical Center, Chongqing 400000, China.
authors: Yadong
authors: Y
authors: Luo
authors: Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
authors: Jianqing
authors: J
authors: Xu
authors: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Hai
authors: H
authors: Qi
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Yuzhang
authors: Y
authors: Wu
authors: Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
authors: Lilin
authors: L
authors: Ye
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D002454:Cell Differentiation; D002908:Chronic Disease; D005260:Female; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000254:growth & development / Q000276:immunology*; D008297:Male; D051379:Mice; D054380:Receptors, CXCR5 / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051797:Inhibitor of Differentiation Protein 2; D054380:Receptors, CXCR5; C513179:CXCR5 protein, mouse; C497452:Idb2 protein, mouse; C075668:Tcf3 protein, mouse