γδ T Cells Contribute to the Outcome of Murine Fulminant Viral Hepatitis via Effector Cytokines TNF-α and IFN-γ
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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.
Key wordsfulminant viral hepatitis murine hepatitis virus strain 3 gamma delta T cell receptors T cells tumor necrosis factor-α interferon-γ
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- 15.Liu H, Zheng T, Mao Y, et al. γδ T cells enhance B cells for antibody production in Hashimoto’s thyroiditis, and retinoic acid induces apoptosis of the Yô T cell. Endocrine. 2016, 51(1), 113–122Google Scholar
- 21.Hui CK, Lau GK. Immune system and hepatitis B virus infection. J Clin Virol, 2005, 34 Suppl 1:S44–S48Google Scholar
- 28.Tseng CT, Miskovsky E, Houghton M, et al. Characterization of liver T-cell receptor gamma delta T cells obtained from individuals chronically infected with hepatitis C virus (HCV): evidence for these T cells playing a role in the liver pathology associated with HCV infections. Hepatology, 2001, 33(5):1312–1320CrossRefPubMedGoogle Scholar
- 30.Jaruga B, Hong F, Kim WH, et al. IFN-gamma/STAT1 acts as a proinflammatory signal in T cell-mediated hepatitis via induction of multiple chemokines and adhesion molecules: a critical role 655 of IRF-1. Am J Physiol Gastrointest Liver Physiol, 2004, 287(5):G1044–G1052Google Scholar
- 32.Zheng T, Zhao W, Li H, et al. p38a signaling in Langerhans cells promotes the development of IL-17-producing T cells and psoriasiform skin inflammation. Sci Signal, 2018, 11(521)Google Scholar
- 33.Kim G, Gu MJ, Kim SJ, et al. Transcription Factor KLF10 Constrains IL-17-Committed Vy4+ yôT Cells. Front Immunol, 2018, 9:196Google Scholar