CD56明亮的自然杀伤细胞通过诱导HBsAg清除 细胞溶解和非细胞

StephenW

EASL 2018 FRI-334
CD56 bright natural killer cell induces HBsAg clearance via
Cytolysis and non-cytolysis: Analysis of the OSST patient dataset
A. Shi, X. Zhang, F. Xiao, L. Zhu, W. Yan, M. Han, T. Chen, Q. Ning. Tongji
Hospital, Tongji Medical College, Huazhong University of Science and
Technology, Department and Institute of Infectious Disease
Email: [email protected]
Background and Aims: HBV surface antigen (HBsAg) reduction is
Well observed in chronic hepatitis B (CHB) patients treated with
Pegylate interferon-alpha-2a (Peg-IFNα). However, the mechanismof
HBsAg suppression has not been fully elucidated.
Method: Twenty-seven of 55 Entecavir-treated CHB e antigen
Positive patients were switched to Peg-IFNα treatment (Group A)
But 28 patients continued entecavir treatment (Group B). The
Percentage or absolute number of CD56bright/CD56dim NK cells,
Expression of receptors and cytokines were evaluated by flow
Cytometry for 48 weeks and correlated with treatment efficacy. In
Vitro, purified NK cells were co-cultured with HepAD38 cells for
Measurement of HBsAg, apoptosis and covalently closed circular DNA
(cccDNA).
Results: In association with a reduction of HBsAg, the percentage and
Absolute number of CD56bright NK cell was significantly elevated in
patients in group A, especially in Virologic Responders (VRs, HBsAg
decreased). Furthermore, percentage of NKp30+, NKp46+, TRAIL+,
TNF-α+ and IFNγ+CD56bright NK cells were significantly expanded in
Group A, which were positively correlated with the decline of HBsAg
atweek 48. In Vitro, peripheral NK cells fromGroup A induced decline
of HBsAg in comparison with NK cells from Group B which was
significantly inhibited by anti-TRAIL, anti-TNF-α and anti-IFNγ
antibodies. Furthermore, apoptosis of HepAD38 cells and levels of
cccDNA, were significantly reduced by TRAIL+ and TNF-α+/IFNγ+NK
cells from Group A respectively.
Conclusion: A functional restoration of CD56bright NK cells in
Entecavir-treated patients who were switched to Peg-IFNα contributes
to HBsAg and cccDNA clearance through TRAIL-induced
cytolysis and TNF-α/IFNγ-mediated noncytolytic pathways.

StephenW

EASL 2018 FRI-334
CD56明亮的自然杀伤细胞通过诱导HBsAg清除
细胞溶解和非细胞溶解：分析OSST患者数据集
A. Shi，X. Zhang，F. Xiao，L. Zhu，W. Yan，M. Han，T. Chen，Q. Ning。同济
华中科技大学同济医学院附属医院
技术，系和传染病研究所
电子邮件：[email protected]
背景和目标：HBV表面抗原（HBsAg）的减少是
观察慢性乙型肝炎（CHB）患者治疗
聚乙二醇干扰素-α-2a（Peg-IFNα）。但是，机制
HBsAg抑制尚未完全阐明。
方法：55例恩替卡韦治疗的CHB e抗原中的27例
阳性患者转为Peg-IFNα治疗（A组）
但有28例患者继续使用恩替卡韦治疗（B组）。该
CD56bright / CD56dim NK细胞的百分比或绝对数量，
通过流动评估受体和细胞因子的表达
细胞计数为48周并与治疗效果相关。在
将体外纯化的NK细胞与HepAD38细胞共培养
测量HBsAg，细胞凋亡和共价闭合环状DNA
（cccDNA的）。
结果：与HBsAg减少，百分比和
CD56bright NK细胞的绝对数量明显升高
A组患者，尤其是病毒学应答者（VRs，HBsAg）
减少）。此外，NKp30 +，NKp46 +，TRAIL +，
TNF-α+和IFNγ+ CD56bright NK细胞显着扩增
A组与HBsAg下降呈正相关
atweek 48.体外，来自A组的外周NK细胞诱导下降
的HBsAg与B组NK细胞相比较
被抗TRAIL，抗TNF-α和抗IFNγ显着抑制
抗体。此外，HepAD38细胞凋亡和水平
cccDNA，TRAIL +和TNF-α+ /IFNγ+ NK均显着降低
来自A组的细胞。
结论：CD56bright NK细胞体外功能恢复
恩替卡韦治疗患者改用Peg-IFNα有助于治疗
通过TRAIL诱导HBsAg和cccDNA清除
细胞溶解和TNF-α/IFNγ介导的非细胞溶解途径。

MP4

宁琴教授 女