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.
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.
ABSTRACT
São descritas as manifestações clinicas, laboratoriais e aspectos evolutivos de cinco pacientes procedentes de Codajás-Amazonas, atendidos no Instituto de Medicina Tropical de Manaus devido ao quadro de hepatopatia grave, com período médio de doença de quatro dias. Quatro destes pacientes evoluiram para óbito, com uma média de cinco dias desde o inicio dos pródromos. A sorologia para hepatite B mostrou que o Ag HBs estava presente em quatro e o Anti - HBc em todos. Dos pacientes que foram ao óbito, através da necropsia a histopatologia do fígado revelou quadro de hepatite fulminante em dois e de febre de Lábrea nos outros dois.
We have described the clinical and laboratory manifestations and evolutiortal aspects of five patients from Codajás, state of Amazonas, Brasil. These patients were treated at the Instituto de Medicina Tropical de Manaus with a picture of acute liver failure with an average period of evolution of 4 days. Of these patients, four died, within an average time of five days since the prodromal phase. Serology for hepatitis B showed that HBAg was present in four, and the HBc antigen in all patients. An autopsy was perfomed on the four patients who died, and the liver histopathology revealed a picture of fulminant hepatitis in two, and Lábrea fever (febre negra), in the other two.