EB病毒BLLF-1基因转染小鼠T细胞淋巴瘤的研究

目的:研究EBV膜蛋白gp350/220的表达对共刺激分子ICOS的影响以及与T细胞淋巴瘤的关系。方法:繁殖饲养BLLF-1转基因昆明鼠以及正常昆明鼠,观察它们淋巴瘤发病率的差异。取发病的BLLF-1转基因昆明鼠脾脏淋巴细胞,用FITC标记的抗gp350/220单克隆抗体进行免疫荧光染色,检测gp350/220是否在该转基因昆明鼠淋巴细胞内表达及其表达部位。对发病转基因昆明鼠组织进行免疫组化染色,并与正常昆明鼠的进行对比分析。用RT-PCR方法检测转基因小鼠共刺激分子ICOS的表达变化。结果:BLLF-1转基因昆明鼠淋巴组织病理性改变与正常昆明鼠有显著差异,免疫荧光检测到该转基因小鼠淋巴细胞表达gp350/220于胞浆和胞膜上,病理学观察发现,发病小鼠淋巴结组织有反应性增生,脾脏淋巴瘤细胞浸润,免疫组化证明为T细胞淋巴瘤,转基因小鼠脾脏、肺脏及肿瘤中ICOS表达显著升高。结论:BLLF-1基因的表达,与该转基因小鼠发生T细胞淋巴瘤有关,并引起共刺激分子ICOS表达的变化,该转基因小鼠的建立,为我们进一步研究BLLF-1基因在T细胞淋巴瘤发病中的作用提供了良好的动物模型。

Study on T Cell Lymphoma in Epstein-Barr Virus BLLF-1 Gene Transgenic Mice

Objective:To study whether the expression ofEBV BLLF-1 gene activates the co-stimulatory molecules ICOS and in- duces T cells lymphoma.Methods:The localization of expressed products in the lymphocytes was determined by confocal microscopy, and HE staining was carried out to identify the changes in the lymph nodes of BLLF-1 transgenic mice.The immunophenotype of lym- phoma cells was analyzed by immunohistochemistry.RT-PCR was used to detect the change of costimulatory molecules ICOS.Results: Immunofluorescencc analysis confirmed that the expressed gp350/220 localized in the cytoplasm and on the membrane of lymphocytes. Pathological results showed hyperplasia of spleen in the transgenic mice.T cells lymphoma was confirmed by immunohistochemistry.The expression of ICOS increased significantly in the spleen,lung and tumor of the transgenic mice.Conclusion:The expression of BLLF-1 gene is related to the development of lymphoma in the transgenic mice,and may affect the level of IOCS expression.BLLF1 gene is like- ly to be an oncogene for lymphoma.