Pegylated Interferon-ɑ (IFN-ɑ) Enhances the Inhibitory Effect of Natural Killer Cells on Regulatory T Cells via IFN-γ in Chronic Hepatitis B.

The immunomodulatory role of natural killer (NK) cells has been recognized recently, but its effects on CD4+CD25+ regulatory T cells (Tregs) during chronic hepatitis B (CHB) infection and treatment remain unclear. A total of 116 nucleos(t)ide analogue (NA)-treated CHB patients were included. An inverse correlation between the peripheral frequencies of NK cells and Tregs was found in NA suppressed patients following pegylated interferon-ɑ (PegIFN-ɑ)-based treatment. Furthermore, NK cells suppressed the proliferation and differentiation of Tregs through secreting IFN-γ as was evidenced in the circulation of NA-treated CHB patients as well as in liver of HBV-carrier mouse model. Additionally, the inhibition could be enhanced by PegIFN-ɑ treatment, which was correlated to more vigorous HBV-specific T-cell responses and marked reduction in HBsAg. Our study reveals a novel immunomodulatory mechanism of NK cells and provides a theoretical basis for PegIFN-ɑ as an immunotherapy agent in treating patients with CHB.