J Infect Dis. 2018 Sep 27. doi: 10.1093/infdis/jiy576. [Epub ahead of print]
Interleukin-21 Reinvigorates the Antiviral Activity of Hepatitis B Virus (HBV)-Specific CD8+ T Cells in Chronic HBV Infection.
Tang L1, Chen C1, Gao X1,2, Zhang W1, Yan X1,3, Zhou Y1, Guo L1, Zheng X1, Wang W1, Yang F4, Liu G4, Sun J1, Hou J1, Li Y1.
Author information
1
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
2
Department of Hepatology, Huizhou Municipal Central Hospital, Huizhou, China.
3
Department of Infectious Diseases and Hepatology Unit, Huadu District People's Hospital of Guangzhou, Guangzhou, China.
4
Liver Disease Research Center, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China.
Abstract
Background:
Strategies that target functional recovery of exhausted hepatitis B virus (HBV)-specific CD8 + T cells are beneficial for viral control, but the potential for interleukin (IL)-21 to rescue CD8 + T cell function is not well understood.
Methods:
We investigated the effect of IL-21 on CD8+ T cell responses by phenotypic and functional analysis of samples from patients with chronic HBV infection and mouse model with HBV expression.
Results:
IL-21 promoted the proliferative capacity of HBV-specific CD8+ T cells and downregulated expression of inhibitory receptors programmed death-1 and T cell immunoglobulin domain and mucin domain 3. Additionally, IL-21 boosted the production of interferon-γ, granzyme B, and CD107a in HBV-specific CD8+ T cells and enhanced the cytolytic activity of CD8+ T cells against HepG2.2.15 cells. Notably, an HBV mouse model established from IL-21 receptor knockout mice showed significantly decreased frequency of HBV-specific CD8+ T cells and increased levels of serum HBsAg. Meanwhile, administration of recombinant mouse IL-21 in an HBV mouse model established from wild-type mice resulted in enhanced functionality of HBV-specific CD8+ T cells and accelerated HBsAg clearance.
Conclusions:
IL-21 enhances the antiviral effect of HBV-specific CD8+ T cells, suggesting that it may contribute to viral clearance in chronic HBV infection.
