Changes of Treg and Th17 cells balance in the development of acute and chronic hepatitis B virus infection

Background: Many studies suggest that in chronic hepatitis B virus (HBV) infection regulate T (Treg) cells and interlukin-17-producing T help cells (Th17) are mutually antagonistic in the immune response. This study is aimed to reveal the cell differentiation environment and the significance of Treg and Th17 balance in the development of acute and chronic HBV infection. Methods: Ten patients with acute HBV infection (AHB) and forty-eight patients with chronic HBV infection, including 12 asymptomatic HBV carriers (HBV carriers), 18 chronic hepatitis B patients (CHB) and 18 acute-on-chronic HBV-related liver failure (ACHBLF) were enrolled. Treg and Th17 cells differentiation related cytokine levels were detected by using ELISA. Flow cytometry was employed to count the Treg and Th17 frequency in peripheral blood. Results: Compared to health controls both AHB and ACHBLF patients favoured Th17 cell differentiation, accompanied by a higher proportion of peripheral Th17 cells (P<0.01) and high level of interleukin-17A (IL-17A) (P<0.01). However, asymptomatic HBV carriers and CHB were conducive to Treg cell differentiation. In AHB and ACHBLF, peripheral blood IL-17A+CD4+T cell frequency increased significantly compared with healthy controls. Changes of Treg and Th17 cell frequency were not completely consistent. Both CHB and ACHBLF had lower level of Treg/Th17 ratio than in health control (P<0.05). Both plasm IL-17A levels (r = -0.72, p<0.001) and Th17 frequency (r = -0.49, p = 0.0003) negatively correlated with plasma HBV DNA load in patients with chronic HBV infection. In addition, both Th17 frequency and plasm IL-17A levels positively correlated with ALT (r = 0.33, p = 0.01 Vs r = 0.29, p = 0.04) and total bilirubin levels (r = 0.72, p<0.0001 Vs r = 0.53, p = 0.0001) in these chronic HBV-infected subjects. However, for AHB there were positive correlation between both Th17 frequency (r = 0.64, p = 0.04) and plasm IL-17A levels (r = 0.69, p = 0.02) with serum ALT levels, but no significant correlation between both HBV DNA level and total bilirubin level with Th17 frequency or plasm IL-17A levels were found. Furthermore, Treg/Th17 ratio was negatively correlated with total bilirubin levels (r = -0.41, p = 0.004) in chronic HBV-infected patients, especially in patients with ACHBLF (r = -0.69, p = 0.001) and positively correlated with viral load in these chronic HBV-infected subjects (r = 0.55, p<0.0001). Conclusions: Th17 cells are involved in acute and chronic HBV infection, especially in AHB and ACHBLF. CHB and ACHBLF patients manifested obvious Treg/Th17 ratio imbalance, which might be linked to disease progression and the continuous HBV infection.