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J Infect Dis. 2019 Feb 15;219(5):750-759. doi: 10.1093/infdis/jiy576.

Interleukin 21 Reinvigorates the Antiviral Activity of Hepatitis B Virus (HBV)-Specific CD8+ T Cells in Chronic HBV Infection.

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, Guangzhou, China.
3
Department of Infectious Diseases and Hepatology Unit, Huadu District People's Hospital of Guangzhou, Guangzhou, China.
4
Liver Disease Research Center, 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 21 (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 a mouse model with HBV expression.

RESULTS:

IL-21 promoted the proliferative capacity of HBV-specific CD8+ T cells and down-regulated expression of the 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 hepatitis B surface antigen (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.

KEYWORDS:

CD8+ T cells; hepatitis B virus; interleukin 21

PMID:
30260401
DOI:
10.1093/infdis/jiy576

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