Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection
During chronic viral infection, virus-specific CD8+ T cells become exhausted, exhibit poor effector function and lose memory potential1,2,3,4. However, exhausted CD8+ T cells can still contain viral replication in chronic infections5,6,7,8,9, 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.
Authors: 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
Influence Factor: 40.137
Citation: Nature 537, 412-428 (2016).Read entire article