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HBsAg和HBcAb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（rmIFN-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HBsAg、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HBsAg水平较高并能检测到HBcAb，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HBsAg水平呈负相关，而肝内CD19+B细胞频数与血清HBcAb水平呈正相关；rmIFN-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。

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

  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 HBsAg, HBcAb, 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 (rmIFN-α) ａnd another 9 transgenic mice were injected with PBS, ａnd their HBsAg, 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 HBsAg with a detectable level of HBcAb 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 HBsAg level while a positive correlation between intrahepatic CD19(+) B cell frequency ａnd HBcAb level were found in HBV transgenic mice. Administration of rmIFN-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.

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