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Nature. 2016 Aug 2;537(7620):412-428. doi: 10.1038/nature19317.

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

Author information

Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, Beijing 100084, China.
Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
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.
Department of Anatomy, School of Basic Medicine, Third Military Medical University, Chongqing 400038, China.
Department of Oncology, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China.
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Chongqing Public Health Medical Center, Chongqing 400000, China.


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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