HBsAg 刺激自然杀伤细胞上的 NKG2D 受体表达并抑制丙型肝炎病毒复制。
HBsAg stimulates NKG2D receptor expression on natural killer cells and inhibits hepatitis C virus replication.
机构信息
Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing 100044, China.
Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing 100044, China.
出版信息
Hepatobiliary Pancreat Dis Int. 2018 Jun;17(3):233-240. doi: 10.1016/j.hbpd.2018.03.010. Epub 2018 Mar 26.
BACKGROUND
Higher hepatitis B surface antigen (HBsAg) facilitates hepatitis C virus (HCV) clearance in patients with hepatitis B virus (HBV)/HCV co-infection. We investigated the effect of exogenous HBsAg on the inhibition of HCV replication mediated by natural killer (NK) cells.
METHODS
After isolated from peripheral blood of 42 chronic hepatitis B (CHB) patients and 16 healthy individuals, NK cells were co-cultured with HCV-infected Huh7 cells, respectively, with or without HBsAg. Three days later, the co-cultured supernatants were collected and HCV RNA levels were measured by real-time quantitative PCR. NKG2D, NKp46 and NKG2A expression levels were measured by flow cytometry. NKG2D on NK cells from CHB responsive subgroup was blocked and HCV RNA levels were examined again.
RESULTS
HCV RNA levels in the co-cultured system were significantly reduced by NK cells isolated from healthy donors (P < 0.01) but not from CHB patients. However, HCV RNA levels in CHB cultures were significantly decreased following HBsAg addition (P < 0.05), whereas no such effect was seen in control cultures. No significant difference was observed in basic NKG2D expression between the CHB patients and healthy donors. On NK cells from CHB patients, the expression of NKG2D was increased significantly by HBsAg stimulation (P < 0.01), and higher than that from healthy controls (P < 0.05). HCV RNA levels were increased significantly after the blockage of NKG2D on NK cells from responsive CHB patients in the co-cultured system (P < 0.05).
CONCLUSION
Exogenous HBsAg stimulated NKG2D expression on NK cells from CHB patients which inhibit HCV replication, suggesting that HBsAg may facilitate the clearance of HCV in patients with HBV/HCV co-infection.
背景
较高的乙型肝炎表面抗原（HBsAg）有助于乙型肝炎病毒（HBV）/丙型肝炎病毒（HCV）合并感染患者清除丙型肝炎病毒（HCV）。我们研究了外源性 HBsAg 对自然杀伤（NK）细胞介导的 HCV 复制抑制的影响。
方法
从 42 例慢性乙型肝炎（CHB）患者和 16 名健康个体的外周血中分离 NK 细胞，分别与 HCV 感染的 Huh7 细胞共培养，有或没有 HBsAg。3 天后，收集共培养上清液，实时定量 PCR 检测 HCV RNA 水平。流式细胞术检测 NKG2D、NKp46 和 NKG2A 的表达水平。用 NK 细胞表面的 NKG2D 阻断 CHB 反应亚组的 NK 细胞，再次检测 HCV RNA 水平。
结果
来自健康供体的 NK 细胞（P < 0.01）而非 CHB 患者的 NK 细胞共培养系统中 HCV RNA 水平显著降低。然而，HBsAg 加入 CHB 培养物后 HCV RNA 水平显著降低（P < 0.05），而对照培养物中未见这种作用。CHB 患者与健康供体之间基本 NKG2D 表达无显著差异。在 CHB 患者的 NK 细胞上，HBsAg 刺激可显著增加 NKG2D 的表达（P < 0.01），且高于健康对照（P < 0.05）。在共培养系统中，对 NK 细胞表面的 NKG2D 进行阻断后，反应性 CHB 患者的 NK 细胞中 HCV RNA 水平显著增加（P < 0.05）。
结论
外源性 HBsAg 刺激 CHB 患者 NK 细胞表面 NKG2D 的表达，抑制 HCV 复制，提示 HBsAg 可能有助于 HBV/HCV 合并感染患者清除 HCV。
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