期刊
NATURE
卷 537, 期 7620, 页码 412-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature19317
关键词
-
资金
- National Basic Research Program of China (973 program) [2013CB531500, 2014CB542501]
- National Natural Science Foundation of China [81220108024, 81471624, U1202228, 81425011, 81330070, 31500733]
During chronic viral infection, virus-specific CD8(+) T cells become exhausted, exhibit poor effector function and lose memory potential(1-4). However, exhausted CD8(+) T cells can still contain viral replication in chronic infections(5-9), 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(+) 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(+) 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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