HBV转基因小鼠体内淋巴细胞表型特点及干扰素α对其的影响  

Characteristics of lymphocyte phenotypes in HBV transgenic mice and the effect of interferon-α: a preliminary study

作　　者：严鑫[1] 钟锐华[1] 刘锦红[1] 周扬[1] 唐利波[1] 李咏茵[1] 刘光泽 侯金林[1] 

机构地区：[1]器官衰竭防治国家重点实验室//广东省病毒性肝炎研究重点实验室//南方医科大学南方医院感染内科,广东广州510515 [2]广州市解放军458医院全军肝病中心//转基因工程研究室,广东广州510602

出　　处：《南方医科大学学报》2016年第6期870-874,共5页Journal of Southern Medical University

基　　金：广东省自然科学基金(2015A030310440)

摘　　要：目的探讨乙型肝炎病毒(HBV)转基因小鼠体内淋巴细胞表型特点及干扰素α对其病毒学指标和免疫细胞表型的影响。方法选取HBV转基因小鼠和野生型(WT)小鼠,采用ELISA检测HBV转基因小鼠血清HBs Ag和HBc Ab水平及两组小鼠血清IL-21及IL-6水平,分离肝、脾以及外周血淋巴细胞,流式细胞术检测CD4+T和CD19+B细胞频数;给予9只HBV转基因小鼠重组鼠源性干扰素α(rm IFN-α)皮下注射,同时9只HBV转基因小鼠相应注射PBS,观察其血清HBs Ag、HBV DNA、IL-6、IL-21水平的变化以及外周血CD4+T和CD19+B细胞频数变化。结果 HBV转基因小鼠的血清HBs Ag水平较高并能检测到HBc Ab,其血清IL-21及IL-6水平较WT小鼠显著升高(P<0.05);HBV转基因小鼠外周血、肝脏以及脾脏淋巴细胞中CD4+T细胞频数较WT小鼠均明显低下(P<0.05),但其肝脏CD19+B细胞频数明显高于WT小鼠(P<0.05);HBV转基因小鼠肝内CD4+T细胞频数与血清HBs Ag水平呈负相关,而肝内CD19+B细胞频数与血清HBc Ab水平呈正相关;rm IFN-α处理可显著提高HBV转基因小鼠外周血CD4+T和CD19+B细胞频数以及血清IL-6水平(P<0.05)。结论 HBV转基因小鼠体内淋巴细胞亚群频数异常,外源性干扰素α可通过调节淋巴细胞亚群频数发挥免疫调节作用。Objective To analyze the characteristics of lymphocyte phenotypes in hepatitis B virus（HBV） transgenic mice and the effect of exogenous interferon-α on virological profiles and lymphocytes phenotypes of the mice. Methods HBV transgenic mice and wild- type（WT） mice were examined for serum levels of HBs Ag, HBc Ab, IL- 21, and IL- 6 using ELISA. The frequencies of CD4^＋T and CD19^＋B cells separated from the liver, spleen, and peripheral blood were detected by flow cytometry.Nine HBV transgenic mice were injected subcutaneously with recombinant mouse interferon alpha（rm IFN- α） and another 9transgenic mice were injected with PBS, and their HBs Ag, HBV DNA, IL- 6, and IL- 21 levels and frequencies of peripheral blood CD4^＋T and CD19^＋B cells were detected. Results HBV transgenic mice showed a high level of HBs Ag with a detectable level of HBc Ab and significantly increased serum levels of IL-21 and IL-6 as compared with WT mice（P〈0.05）. The transgenic mice had a significantly lower frequency of CD4^＋T cells in the peripheral blood, liver and spleen（P〈0.05） but a significantly higher frequency of CD19^＋B cells in the liver（P〈0.05）. An inverse correlation between intrahepatic CD4^＋T cell frequency and serum HBs Ag level while a positive correlation between intrahepatic CD19^＋B cell frequency and HBc Ab level were found in HBV transgenic mice. Administration of rm IFN- α significantly increased the frequencies of CD4^＋T and CD19^＋B cells in the peripheral blood and the serum level of IL- 6 in HBV transgenic mice（P〈0.05）. Conclusion HBV transgenic mice have lymphocyte subset dysregulation and exogenous interferon-α can modulate the immune function of the mice by regulating the frequencies of lymphocyte subsets.

关 键 词：乙型肝炎病毒 转基因小鼠 干扰素Α 免疫调节 

分 类 号：R512.62[医药卫生—内科学]