摘要

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