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...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-y （IFN-3,） 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. Key words： fulminant viral hepatitis; murine hepatitis virus strain 3; gamma delta T cell receptors T cells; tumor necrosis factor-a; interferon-α展开更多
基金This project was supported by grants from the Chinese National Thirteenth Five Years Project in Science and Technology （No. 2017ZX10202201）, and Hubei Provincial Natural Science Foundation of China （No. 2018CFB206）.
文摘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-y （IFN-3,） 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. Key words： fulminant viral hepatitis; murine hepatitis virus strain 3; gamma delta T cell receptors T cells; tumor necrosis factor-a; interferon-α
