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.
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].