【摘要】 目的探讨HBV感染对肝脏自然杀伤细胞(NK细胞)和固有淋巴样细胞(ILC)22的影响,为阐明HBV感染诱导机体固有免疫应答的机制提供理论和实验依据。方法选取6~8周龄雄性BALB/c小鼠10只,随机分为实验组和对照组,每组各5只。实验组小鼠经尾静脉高压注射含10μg HBV全基因组质粒的生理盐水(体积相当于9%小鼠体质量);对照组小鼠仅注射生理盐水。4 d后处死小鼠,分离肝脏内淋巴细胞,应用流式细胞术检测肝脏内淋巴细胞中NK细胞亚群和ILC22细胞亚群的比例。组间比较采用t检验。结果高压尾静脉注射HBV全基因组质粒可诱导小鼠产生高水平的HBs Ag和HBe Ag,伴有血清ALT水平升高。实验组小鼠肝脏内NK细胞的比例较对照组小鼠显著升高[(25.90±4.92)%vs(12.98±2.13)%,t=3.811,P=0.003],但CD127+NK细胞和CD127-NK细胞亚群在NK细胞中所占比例在2组之间差异均无统计学意义(P值均>0.05)。实验组小鼠肝脏内NKp46+ILC22细胞亚群比例较对照组明显升高[(36.05±6.85)%vs(10.22±3.54)%,t=7.372,P<0.001],但NKp46-ILC22细胞亚群的比例在2组之间差异无统计学意义(P>0.05)。结论 HBV感染可诱导肝脏内NK细胞和NKp46+ILC22水平升高,从而促进肝脏固有免疫应答。更多还原

【Abstract】 Objective To investigate the influence of hepatitis B virus( HBV) infection on intrahepatic natural killer( NK) cells and innate lymphoid cell 22( ILC22),and to provide theoretical and experimental bases for clarifying mechanisms of HBV infection in inducing innate immune response. Methods A total of 10 male BALC / c aged 6-8 weeks were divided into experimental group and control group,with 5 mice in each group. The mice in the experimental group were treated with the hydrodynamic injection of normal saline containing 10μg plasmids of complete HBV genome( the volume equaled to 9% of the body weight of the mouse) via the caudal vein,and those in the control group were only treated with normal saline. The mice were scarified 4 days later,and intrahepatic lymphocytes( IHLs) were isolated.Flow cytometry was used to determine the proportions of NK cells and ILC22 subset in IHLs,and the t-test was used for comparison between groups. Results Hydrodynamic injection of the plasmids containing complete HBV genome induced high levels of HBs Ag and HBe Ag in mice,with an increase in the serum level of alanine aminotransferase. After HBV infection,the experimental group showed a significant increase in the proportion of intrahepatic NK cells compared with the control group( 25. 90% ± 4. 92% vs 12. 98% ± 2. 13%,t = 3. 811,P =0. 003),while there were no significant differences in the proportions of CD127+and CD127-NK subsets in NK cells between the two groups. Moreover,after HBV infection,the experimental group showed a significant increase in the proportion of intrahepatic NKp46+ILC22subset compared with the control group( 36. 05% ± 6. 85% vs 10. 22% ± 3. 54%,t = 7. 372,P < 0. 001); however,there was no significant difference in the proportion of NKp46-ILC22 between the two groups. Conclusion HBV infection induces increased levels of intrahepatic NK cells and NKp46+ILC22 cells and thus promotes the innate immune response in the liver.更多还原