The First Operating Room, First Hospital of Jilin University, Changchun, China.
Neurosurgical Intensive Care Unit, First Hospital of Jilin University, Changchun, China.
Viral Immunol. 2022 Jan-Feb;35(1):41-49. doi: 10.1089/vim.2021.0140. Epub 2021 Nov 24.
Restoration of exhausted hepatitis B virus (HBV)-specific CD8 T cells is one of the important strategies for inhibition of viral replication. The role of interleukin (IL)-33 to recovery of CD8 T cell activity is not fully elucidated. We investigated the effect of IL-33 on viral-specific CD8 T cell responses in chronic hepatitis B (CHB) patients by both phenotypic and functional analysis. Plasma IL-33 was downregulated in CHB patients, while effective antiviral therapy rescued IL-33 expression. There was no significant difference of IL-33 receptor mRNA relative level in CD8 T cells between CHB patients and controls. IL-33 induced the proliferation of HBV-specific CD8 T cells, and reduced programmed death-1 expression on HBV-specific CD8 T cells. IL-33 promoted the direct cytolytic activity of CD8 T cells against HepG2.2.15 cells through boosting perforin and granzyme B production. Furthermore, IL-33 administration increased HBV-specific CD8 T cell-mediated HBV replication and HBV antigen secretion mainly via enhancement of interferon- and tumor necrosis factor-. IL-33 reinvigorated antiviral activity of HBV-specific CD8 T cells, revealing that IL-33 might contribute to viral clearance in persistent HBV infection.
恢复耗尽的乙型肝炎病毒 (HBV)-特异性 CD8 T 细胞是抑制病毒复制的重要策略之一。白细胞介素 (IL)-33 对 CD8 T 细胞活性的恢复作用尚未完全阐明。我们通过表型和功能分析研究了 IL-33 对慢性乙型肝炎 (CHB) 患者病毒特异性 CD8 T 细胞反应的影响。CHB 患者的血浆 IL-33 下调，而有效的抗病毒治疗可恢复 IL-33 的表达。CHB 患者和对照组 CD8 T 细胞中 IL-33 受体 mRNA 的相对水平无显著差异。IL-33 诱导 HBV 特异性 CD8 T 细胞增殖，并降低 HBV 特异性 CD8 T 细胞上程序性死亡-1 的表达。IL-33 通过促进穿孔素和颗粒酶 B 的产生来促进 CD8 T 细胞对 HepG2.2.15 细胞的直接细胞毒性作用。此外，IL-33 给药增加了 HBV 特异性 CD8 T 细胞介导的 HBV 复制和 HBV 抗原分泌，主要通过增强干扰素和肿瘤坏死因子的产生。IL-33 增强了 HBV 特异性 CD8 T 细胞的抗病毒活性，表明 IL-33 可能有助于清除持续性 HBV 感染。
