Peg IFN-ɑ Treatment Enhanced the Inhibitory Effect of NK Cells on the Differentiation and Proliferation of CD4 +CD25 + Tregs 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 Peg IFN-ɑ-based treatment. Further, NK cells suppressed the proliferation and differentiation of Tregs through secreting IFN-γ was evidenced in the circulation of NA-treated CHB patients as well as in the liver of HBV-carrier mouse model. Additionally, the inhibition could be enhanced by Peg IFN-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 Peg IFN-ɑ as an immunotherapy agent in treating patients with CHB.