Interleukin 21 Reinvigorates the Antiviral Activity of Hepatitis B Virus (HBV)-Specific CD8+ T Cells in Chronic HBV Infection
Interleukin 21 Reinvigorates the Antiviral Activity of Hepatitis B Virus (HBV)-Specific CD8+ T Cells in Chronic HBV Infection
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白介素 21 重振慢性 HBV 感染中乙型肝炎病毒 (HBV) 特异性 CD8 T 细胞的抗病毒活性
DOI：
10.1093/infdis/jiy576
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Li Yongyin
中科院分区：
文献类型：
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作者：
Tang Libo;Chen Chengcong;Gao Xueping;Zhang Wanyue;Yan Xin;Zhou Yang;Guo Ling;Zheng Xinchun;Wang Weibin;Yang Fuqiang;Liu Guangze;Sun Jian;Hou Jinlin;Li Yongyin
背景以衰竭的B病毒（HBV）特异性CD 8 +T细胞的功能恢复为目标的策略有利于病毒控制，但白细胞介素21（IL-21）拯救CD 8 + T细胞功能的潜力还不清楚。通过对慢性HBV感染患者和HBV表达小鼠模型的样本进行表型和功能分析，21促进HBV特异性CD 8 +T细胞的增殖能力，并下调抑制性受体程序性死亡1和T细胞免疫球蛋白结构域和粘蛋白结构域3的表达。此外，IL-21促进HBV特异性CD 8 +T细胞中干扰素-γ、颗粒酶B和CD 107 a的产生，并增强CD 8 +T细胞对HepG2.2.15细胞的细胞溶解活性。值得注意的是，从IL-21受体敲除小鼠建立的HBV小鼠模型显示HBV特异性CD 8 +T细胞的频率显著降低，血清B表面抗原（HBsAg）水平升高。同时，重组小鼠IL-21在HBV小鼠模型建立从野生型小鼠导致HBV特异性CD 8 +T细胞的功能增强和加速HBsAg clearation.ConclusionsIL-21增强HBV特异性CD 8 +T细胞的抗病毒作用，这表明它可能有助于慢性HBV感染的病毒清除。
BackgroundStrategies 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.MethodsWe 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.ResultsIL-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.ConclusionsIL-21 enhances the antiviral effect of HBV-specific CD8+T cells, suggesting that it may contribute to viral clearance in chronic HBV infection.