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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

1
Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
2
Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, Beijing 100084, China.
3
Shanghai Public Health Clinical Center &Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
4
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.
5
Department of Anatomy, School of Basic Medicine, Third Military Medical University, Chongqing 400038, China.
6
Department of Oncology, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China.
7
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
8
Chongqing Public Health Medical Center, Chongqing 400000, China.

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.

PMID:
27501245
DOI:
10.1038/nature19317
[Indexed for MEDLINE]

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