Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Curr Med Sci. 2018 Aug;38(4):648-655. doi: 10.1007/s11596-018-1926-x. Epub 2018 Aug 20.
The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated. In this study, we investigated the role of gamma delta T cell receptors (γδ) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3). The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice. The survival days of mice, and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined. The proportions of γδ T cells in blood, spleen and liver, and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry. The function of hepatic γδ T cells was examined by cytotoxicity assay. Balb/cJ mice died in 3 to 6 days post MHV-3 infection, with severe hepatic necrosis and significant augmentation of serum ALT and AST levels. The proportions of γδ T cells in blood, spleen and liver were significantly increased post MHV-3 infection, while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ) increased remarkably in the liver. These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway. These results demonstrated that γδ T cells might contribute to the pathogenesis of MHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ.
病毒诱导的重型肝炎的发病机制尚未完全阐明。本研究旨在探讨γδ T 细胞受体（γδ）T 细胞在鼠肝炎病毒 3 株（MHV-3）诱导的暴发性病毒性肝炎（FVH）发病机制中的作用。通过腹腔注射 MHV-3 建立 FVH 模型，观察小鼠的生存天数、血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平，采用流式细胞术分析血液、脾脏和肝脏中 γδ T 细胞的比例以及肝 γδ T 细胞分泌的细胞因子，通过细胞毒性测定检测肝 γδ T 细胞的功能。Balb/cJ 小鼠在感染 MHV-3 后 3 至 6 天内死亡，伴有严重的肝坏死和显著增加的血清 ALT 和 AST 水平。感染 MHV-3 后，血液、脾脏和肝脏中 γδ T 细胞的比例显著增加，而肝脏中早期激活分子 CD69 表达的 γδ T 细胞的比例和细胞因子肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的产生明显增加。这些高度活化的肝 γδ T 细胞在体外对 MHV-3 感染的肝细胞具有细胞毒性，肝 γδ T 细胞对肝细胞的这种作用可能涉及 TNF-α 和 IFN-γ 途径。这些结果表明，γδ T 细胞可能通过效应细胞因子 TNF-α 和 IFN-γ 参与 MHV-3 诱导的 FVH 的发病机制。
