Increase in liver γδ�T�cells with concurrent augmentation of IFN‑β production during the early stages of a mouse model of acute experimental hepatitis B virus infection

Abstract

The role of γδ T cells in acute hepatitis B virus (HBV) infection remains unclear. For the present study, a mouse model of acute HBV infection was constructed using hydrodynamic injection-based transfection of an HBV DNA plasmid (pHBV). Subsequent changes in the percentages of γδ T cells, expression of activation molecules (CD25 and CD69) and the production of the inflammatory cytokines interferon (IFN)-γ and tumor necrosis factor-α (TNF-α) by liver γδ T cells were investigated using fluorescence-activated cell sorting (FACS). Additionally, the immune responses in the mouse liver were evaluated dynamically by measuring cytokine mRNA expression (IFN-α, IFN-β, IFN-γ or TNF-α) using reverse transcription-quantitative PCR, and other populations of immune cells, including CD4+T, CD8+T, natural killer (NK) or natural killer T (NKT) cells, using FACS. On day 1 following acute HBV infection, the percentage of liver γδ T cells was significantly increased along with the high expression of HBV markers. Additionally, liver γδ T cells displayed peak expression of the activation marker CD69 and peak IFN-γ production within this timeframe. IFN-β mRNA expression and the percentage of NK cells were elevated significantly on day 1 in liver tissues. However, there were no significant changes in the spleen or peripheral γδ T cells. Therefore, these data suggested that during the early stages of acute HBV infection, significantly increased numbers of liver γδ T cells may be involved in the enhanced immune response to the increased expression of HBV markers in the liver.

The Roles of γδ T Cells in Hematopoietic Stem Cell Transplantation

“…It shows that in chronic hepatitis B (CHB), Vδ2 T cells decrease in patients’ peripheral blood and relate to less IFN-γ production and cytotoxic activity 75 . In a mouse model of acute HBV infection, liver γδ T cells and IFN-β production increased during the early stages of HBV infection, but there were no much changes in peripheral γδ T cells 76 . And IFN-α can enhance the cytotoxic function of peripheral γδ T cells in CHB 77 .…”

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

“…Few studies have addressed the role of γδ T cells and MAIT cells during acute infection. In mouse models of HBV infection, γδ T cells were found in increased numbers in the liver and actively producing IFN-γ during the first days of infection [ 118 ]. Furthermore, the transfer of hepatic CXCR3 + CXCR6 + γδ T cells from naïve mice to mice with acute HBV infection led to reduced disease and viral loads [ 119 ].…”

γδ T cells: The potential role in liver disease and implications for cancer immunotherapy

“…28 Patients with acute hepatitis B infections have reduced circulating blood γδ T cells and increased hepatic γδ T cells compared with patients with CHB, which might be explained by the elevation of the liver chemokine, IP-10, and RANTES. 29 Furthermore, in an acute HBVinfected mouse model, Chang et al 30 showed that the proportion of hepatic γδ T cells is significantly increased and the immune reaction to increased expression of HBV markers in the liver is enhanced through the secretion of IFN-γ and IFN-β. The proportion of intrahepatic and circulating γδ T cells among CHB-infected patients is negatively correlated with disease severity.…”