Decreased CD122 on CD56 NK associated with its impairment in asymptomatic chronic HBV carriers with high levels of HBV DNA, HBsAg and HBeAg.

AIMS

NK cells play important roles in inhibiting HBV replication and preventing HBV infection. However, NK-cell dysfunction has not been fully studied in asymptomatic chronic HBV carriers (ASC). This study aims to assess decreased expression of CD122 associated with impaired NK cells and the restoration of NK cells with IL-2 and IL-15 stimulation.

MAIN METHODS

The experiments were performed by flow cytometer, cytotoxicity assay, ELISA and western blotting.

KEY FINDINGS

The reduced CD122 on CD56 NK cells and CD56 NK cells is associated with high levels of HBV DNA, HBsAg or HBeAg in ASCs, in which CD56 NK-cell impairment is observed. Moreover, decreased IFN-γ and degranulation and low cytotoxicity by CD56 NK cells after CD122 blockade were revealed. IL-2 and/or IL-15 can restore impaired CD56 NK cells, together with increased p-STAT5, which can be reversed by CD122 blockade. Additionally, IL-2 or IL-15 can enhance IFN-α2-activated CD56 NK-cell immune responses via up-regulating interferon alpha and beta receptor subunit 2 (IFNAR2).

SIGNIFICANCE

Down-regulated CD122 on CD56 NK cell in ASCs with massive viral antigens and high viremia is associated with its impairment, which can be restored by IL-2 and/or IL-15, or combined with IFN-α2.