CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection
Yongyin Li1,†
, Libo Tang1,†
, Ling Guo1,†
, Chengcong Chen1,†
, Shuqin Gu1
, Yang Zhou1
, Guofu Ye1
, Xiaoyi Li1
, Weibin Wang1
, Xinxin Liao2
, Yu Wang3
, Xiaohong Peng4
, Guangze Liu5
, Xiaoyong Zhang1
, Jian Sun1
, Jie Peng1
, Jinlin Hou1,low asterisk,'Correspondence information about the author Jinlin Hou
Highlights
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CXCR5+CD8+T cells produce higher levels of HBV-specific IFN-γ and IL-21 than CXCR5−CD8+T cells.
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CXCR5+CD8+T cells retain functional capacity in inhibiting HBV replication and supporting B cell antibody production.
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PD1 blockade and exogenous IL-21 enhance production of IFN-γ from CXCR5+CD8+T cells.
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High expression of intrahepatic CXCL13 facilitates CXCR5+CD8+T cell recruitment and promotes immune control of HBV.
Background & Aims
Although CD8+T cell exhaustion hampers viral control during chronic HBV infection, the pool of CD8+T cells is phenotypically and functionally heterogeneous. Therefore, a specific subpopulation of CD8+T cells should be further investigated. This study aims to dissect a subset of CD8+T cells expressing C-X-C motif chemokine receptor 5 (CXCR5) in chronic HBV infection.
Methods
The frequency of CXCR5+CD8+T cells and the levels of C-X-C motif chemokine ligand 13 (CXCL13), a chemokine of CXCR5, were measured in patients with chronic HBV infection. C57BL/6, interleukin (IL)-21 receptor- or B cell-deficient mice were hydrodynamically injected with pAAV-HBV1.2 plasmids. Phenotype and functions of peripheral and intrahepatic CXCR5+ and CXCR5−CD8+T cells were assessed.
Results
CXCR5+CD8+T cells were partially exhausted but possessed a stronger antiviral ability than the CXCR5− subset in patients with chronic HBV infection; moreover, CXCR5+CD8+T cells were associated with a favorable treatment response in patients with chronic hepatitis B (CHB). High levels of CXCL13 from patients with CHB facilitated the recruitment of intrahepatic CXCR5+CD8+T cells, and this subpopulation produced high levels of HBV-specific interferon (IFN)-γ and IL-21. Notably, PD1 (programmed death 1) blockade and exogenous IL-21 enhanced the production of IFN-γ. More strikingly, mice injected with CXCR5+CD8+T cells showed remarkably decreased expression of HBsAg. Additionally, an impaired production of HBV-specific IFN-γ from intrahepatic CXCR5+CD8+T cells was observed in IL-21 receptor- or B cell-deficient mice.
Conclusion
CXCL13 promotes the recruitment of CXCR5+CD8+T cells to the liver, and this subpopulation improves viral control in chronic HBV infection. The identification of this unique subpopulation may contribute to a better understanding of CD8+T cell functions and provide a potential immunotherapeutic target in chronic HBV infection.
Lay summary
Exhaustion of CD8+ T cells is an important factor in the development of chronic hepatitis B virus (HBV) infection. CD8+ T cells expressing the receptor CXCR5 are partially exhausted, but have potent antiviral activity, as they produce high levels of HBV-specific cytokines in chronic HBV infection. Increased expression of CXCL13 within the liver facilitates the recruitment of CXCR5+CD8+T cells and establishes effective immune control of HBV infection.作者: StephenW 时间: 2020-2-15 21:47