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CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection.
- Source :
-
Journal of Hepatology . Mar2020, Vol. 72 Issue 3, p420-430. 11p. - Publication Year :
- 2020
-
Abstract
- • CXCR5+CD8+T cells produce higher levels of HBV-specific IFN-γ and IL-21 than CXCR5−CD8+T cells. • CXCR5+CD8+T cells retain functional capacity in inhibiting HBV replication and supporting B cell antibody production. • PD1 blockade and exogenous IL-21 enhance production of IFN-γ from CXCR5+CD8+T cells. • High expression of intrahepatic CXCL13 facilitates CXCR5+CD8+T cell recruitment and promotes immune control of HBV. 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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *T cells
*T cell receptors
*CHRONIC hepatitis B
*LIVER cells
*HEPATITIS B virus
Subjects
Details
- Language :
- English
- ISSN :
- 01688278
- Volume :
- 72
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 141732338
- Full Text :
- https://doi.org/10.1016/j.jhep.2019.09.031