The dynamic changes of circulating invariant natural killer T cells during chronic hepatitis B virus infection

The protective role of invariant natural killer T cells (iNKTs) against hepatitis B virus (HBV) infection remains controversial. We sought to clarify the role of peripheral iNKT cells during chronic HBV infection. Sixty patients with chronic HBV infection were categorized into an immune tolerance phase (HBV-IT) (n = 16), an immune clearance phase (HBV-IC) (n = 19) and an inactive carrier phase (HBV-IA) (n = 25). Twenty healthy individuals were enrolled as healthy controls. Another 21 HBeAg-positive patients were administrated with entecavir (0.5 mg/day) for 6 months. The percentages of circulating iNKT cells and their IFN-gamma and IL-4 expression levels were examined by flow cytometry. The relationships between serum HBV DNA, ALT levels, the percentages of iNKT cells, and their IFN-gamma and IL-4 levels were analyzed. Compared to healthy controls, the percentage of iNKT cells decreased in HBV-IT, but increased in HBV-IC and HBV-IA. Circulating IFN-gamma-producing iNKT cells gradually increased, whereas IL-4-producing iNKT cells gradually decreased from HBV-IT stage to HBV-IC and HBV-IA stages. The frequency of iNKT cells and their IFN-gamma levels were reversely correlated with viral load. The levels of IL-4 expressed by iNKT cells were positively correlated to viral load and the serum ALT levels. After anti-virus therapy, the percentage of IFN-gamma-producing iNKT cells increased while the percentage of IL-4-producing iNKT cells decreased. During chronic HBV infection, the percentages of peripheral iNKT cells and its cytokines expressions of IFN-gamma and IL-4 showed dynamic changes. The expression levels of IFN-gamma and IL-4 were correlated with the clearance of HBV and liver injury.