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。
Objective: To study whether the expression ofEBV BLLF-1 gene activates the co-stimulatory molecules ICOS and induces T cells lymphoma. Methods: The localization of expressed products in the lymphocytes was determined by confoeal microscopy, and HE staining was carried out to identify the changes in the lymph nodes of BLLF-1 transgenic mice. The immunophenotype of lymphoma cells was analyzed by immunohistochemistry. RT-PCR was used to detect the change of costimulatory molecules ICOS. Results: Immunofluorescenee analysis confirmed that the expressed gp350/220 localized in the cytoplasm and on the membrane of lymphoeytes. Pathological results showed hyperplasia of spleen in the transgenic mice. T cells lymphoma was confirmed by immunohistoehemistry.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 likely to be an oncogene for lymphoma.