Function And Mechanism Of γδ T Cells In Different Stages Of Hepatitis B Virus Infection

Hepatitis B virus infection might causes progressive liver damage and eventually leads to liver cirrhosis and hepatocellular carcinoma. However, the precise immunological mechanisms involving in this process are obscure. γδ T cells comprise a subset of innate immunal T cells and play protective or regulatory role against cancer and viral infections; however, their precise role in patients with hepatitis B infection diseases remains unclear. In this study we discussed phenotypic and functional changes of γδ T cells (as well as the subsets of γδ T cells) in different stages of HBV infection. In chronic hepatitis B patients we analyze the impact of γδ T cells in64immune-activated (IA) patients,22immune-tolerant (IT) carriers and30healthy controls (HCs). The frequencies of peripheral and hepatic Vδ2γδ T cells decreased with disease progression from IT to IA. In IA patients, the decreases in peripheral and intrahepatic frequencies of Vδ2γδ T cells reversely correlated with ALT levels and histological activity index. These activated terminally differentiated meomory phenotypic Vδ2γδ T cells exhibited impaired abilities in proliferation and chemotaxis, while maintained a relative intact LFN-γ production. Importantly, Vδ2γδ T cells, in vitro, significantly suppressed the production of IL-17-producing CD4+T (Th17) cells associated cytokines in both cell contact-dependent and IFN-y-dependent mechanisms. Meanwhile, in acute hepatitis B (AHB) infection, we first characterized the peripheral frequency changes of γδ T cells in different stages of HBV infectious progression:29AHB patients,29CHB patients,15acute-on-chronic liver failure (ACLF) patients and15liver cirrhosis (LC) patients as well as25HC. The frequencies of peripheral γδ T cells significantly decreased in AHB、CHB and ACLF patients (these stage of patients showed significantly inflammatory environment) but not in LC patients compared with HC groups. In AHB patients, the decreased of peripheral γδ T cells reversely correlated with serum ALT levels and these activated terminally differentiated meomory phenotypic y8T cells exhibited impaired abilities in granzyme A secretion. In longitude study, patients in convalescent phase showed clearance of HBV, reduced inflammatory stage, increased frequency of γδ T cells, decreased activated phenotype and decreased expression of inhibitory NK receptor on y8T cells compared with in acute phase. In ConA induced acute liver damage animal model, we found that CD4+T cells might be one of the reasons for liver damage. Above all, this study extend the knowledge of γδ T cells in HBV infection and may provide a novel therapeutic approach for HBV infection patients.