Frequency of Treg in Different Phases of Chronic Hepatitis B Virus (HBV) Infection

Chronic hepatitis B virus (HBV) infection is associated with ineffective antiviral T-cell response while the detailed mechanism remains poorly understood. Recent studies have shown that regulatory T cells (Tregs) may contribute to immune regulation in patients with chronic HBV infection, but their role in disease progress is still unclear. The aims of these studies were: (1) to characterize the frequency of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with chronic HBV infection in different phases; (2) to explore the relationship between the frequency of Tregs and clinical parameters. A total of 69 treatment-naïve patients with chronic HBV infection were enrolled into the study, including 35 in immune tolerance phase [age: 27 (18 - 47) years, HBsAg and HBeAg positive, ALT: 0.55 (0.34 - 0.97) x upper limit of normal (ULN), HBV DNA: 1.55 x 10⁹ (6.30 x 10⁶ - 2.01 x 10¹⁰) copies/ml] and 34 in immune clearance phase [age: 33 (20 - 52) years, HBsAg and HBeAg positive, ALT: 4.13 (1.03 - 49.35) x ULN, HBV DNA: 1.21 x 10⁹ (1.62 x 10⁶ - 4.94 x 10¹⁰) copies/ml]. Tregs in PBMCs were analyzed using flow cytometry and the frequency of Tregs was defined as the percentage of CD4+CD25+Foxp3+ T cells in total CD4+ T cells. The frequency of Tregs was significantly higher in patients with chronic HBV infection in the immune clearance phase than in the immune tolerance phase. Increased Tregs was associated with liver injury. We hypothesized that increased Treg frequency may be a response to severe liver damage mediated by a vigorous immune response to HBV. The role of Tregs in this process may be a double-edged sword, protecting the host against excessive tissue damage on the one hand, while prohibiting immune response to clear the virus on the other hand. Future studies are needed to confirm the hypothesis and to dissect the underlying mechanism before translating Tregs into clinical therapeutic applications.