title: Liver TCRγδ(+) CD3(+) CD4(-) CD8(-) T cells contribute to murine hepatitis virus strain 3-induced hepatic injury through a TNF-α-dependent pathway.
abstract: The mechanisms of each subset of immune cells contributing to the pathogenesis of viral hepatitis remain incompletely understood. In this study, we examined the role of liver CD4(-) CD8(-) (double negative, DN) T cells during murine hepatitis virus strain 3 (MHV-3)-induced hepatitis in C3H/HeJ mice. We demonstrate that predominant population of DN T cells in the liver of healthy or MHV-3-infected mice express TCRγδ(+). The proportion of TCRγδ(+) DN T cells in liver CD3(+) T cells was markedly increased after MHV-3 infection. Adoptive transfer of TCRγδ(+) DN T cells led to dramatically decreased survival in MHV-3-infected mice, accompanied by deteriorated histopathology and elevated ALT and AST levels. It was found that these cells were hyperactivated after MHV-3 infection with a production of TNF-α, IFN-γ, IL-2 and IL-17A. Highly activated liver TCRγδ(+) DN T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect did not require cell-cell contact. Moreover, the cytotoxic effect of liver TCRγδ(+) DN T cells against hepatocytes involves TNF-α pathway, but not IL-17A or IFN-γ. These results indicate that liver TCRγδ(+) DN T cells play a critical role in the liver injury in MHV-3-induced hepatitis, via a TNF-α dependent pathway.
authors: Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. luyulei1984@163.com
authors: Yulei
authors: Y
authors: Lu
authors: Xiaojing
authors: X
authors: Wang
authors: Weiming
authors: W
authors: Yan
authors: Hongwu
authors: H
authors: Wang
authors: Ming
authors: M
authors: Wang
authors: Di
authors: D
authors: Wu
authors: Lin
authors: L
authors: Zhu
authors: Xiaoping
authors: X
authors: Luo
authors: Qin
authors: Q
authors: Ning
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D006517:Murine hepatitis virus / Q000276:immunology / Q000472:pathogenicity*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D020381:Interleukin-17; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma