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 (γ&
delta;)
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 ofγ&
delta;
T cells in
blood,
spleen and
liver,and
cytokines secreted by hepatic γ&
delta;
T cells were analyzed by
flow cytometry.The function of hepatic γ&
delta;
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 γ&
delta; T ceils in
blood,
spleen and
liver were significantly increased post MHV-3
infection,while those of the early activating molecule CD69-expressing γ&
delta;
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 γ&
delta;
T cells were cytotoxic to MHV-3-infected
hepatocytes in vitro and this effect of
liver γ&
delta;
T cells against
hepatocytes might involve the TNF-α and IFN-γ pathway.These results demonstrated that γ&
delta;
T cells might contribute to the pathogenesis ofMHV-3-induced FVH through the effector
cytokines TNF-α and IFN-γ.