γδ T Cells Contribute to the Outcome of Murine Fulminant Viral Hepatitis via Effector Cytokines TNF-α and IFN-γ / 华中科技大学学报（医学）（英德文版）

ABSTRACT

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 ofγδ 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 ceils 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 ofMHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ.