Characteristics of Circulatory γδ T cells in Patients with Symptomatic Chronic Hepatitis B Infection

Hepatitis B is a viral infection that can cause serious liver disease. Chronic hepatitis B (CHB) infection places individuals at higher risk of developing cirrhosis of the liver and hepatocellular cancer. Immune dysfunction, including altered distribution and functional status of T cell immunity, is a contributor to hepatitis B virus (HBV) pathogenesis. In this study, we examined the distribution of circulating γδ T cell subpopulations and levels of cell surface expression of suppressive markers on γδ T cells in individuals with CHB infection and clinical liver disease. A significantly higher proportion of terminally differentiated (TEMRA) (CD27−CD45RA+) γδ T cells along with significantly lower percentages of central memory (CD27+CD45RA−) and effector memory (CD27−CD45RA−) γδ T cells were observed in peripheral blood of these individuals. The expression of exhaustion markers-Tim-3 and Lag-3 was elevated in γδ T cells from CHB-infected individuals compared with healthy controls (HC) and blockade of these exhaustion markers resulted in restoration of interferon gamma (IFN-γ) secretion by γδ T cells. In addition, γδ T cells from CHB patients expressed increased levels of CD69, another important regulator of immune responses. Together, these results suggest that CHB patients with clinical sign of liver disease have TEMRA γδ T cells with a potentially exhausted phenotype that may in turn impair their immunoregulatory role and facilitate pathogenesis of CHB disease.