Decreased CD122 on CD56dim NK associated with its impairment in asymptomatic chronic HBV carriers with high levels of HBV DNA, HBsAg and HBeAg
Decreased CD122 on CD56dim NK associated with its impairment in asymptomatic chronic HBV carriers with high levels of HBV DNA, HBsAg and HBeAg
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CD56(dim) NK 上的 CD122 降低与其在 HBV DNA、HBsAg 和 HBeAg 水平高的无症状慢性 HBV 携带者中的损伤相关
DOI：
10.1016/j.lfs.2018.01.001
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发表时间：
2018-02-15
期刊：
影响因子：
6.1
通讯作者：
Chen, Yu
中科院分区：
文献类型：
--
作者：
Han, Wenzheng;Ni, Qin;Chen, Yu
目的：NK细胞在抑制HBV复制和预防HBV感染中发挥重要作用。然而，nk细胞功能障碍尚未在无症状慢性HBV携带者（ASC）中得到充分研究。本研究旨在评估CD122表达下降与受损NK细胞的关系，以及IL-2和IL-15刺激下NK细胞的恢复。主要方法：采用流式细胞仪、细胞毒性试验、酶联免疫吸附试验和免疫印迹法进行实验。关键发现：CD56(+) NK细胞和CD56（暗）NK细胞上CD122的减少与ASCs中HBV DNA、HBsAg或HBeAg的高水平相关，其中CD56（暗）NK细胞被观察到损伤。此外，CD122阻断后CD56(dim) NK细胞的ifn - γ和脱颗粒降低，细胞毒性降低。IL-2和/或IL-15可以恢复受损的CD56(dim) NK细胞，并增加p-STAT5，这可以通过CD122阻断逆转。此外，IL-2或IL-15可以通过上调干扰素α和β受体亚单位2 （IFNAR2）来增强ifn - α 2激活的CD56(dim) nk细胞免疫应答。意义：在大量病毒抗原和高病毒血症的ASCs中，CD56(dim) NK细胞上CD122的下调与其损伤有关，IL-2和/或IL-15或联合ifn - α 2可恢复其损伤。
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.