【摘要】 目的应用主要组织相容性复合物(MHC)Ⅱ与人TSH受体(TSHR)共表达细胞(hM12细胞)模拟Graves病(GD)时的甲状腺细胞,免疫C57BL/6小鼠,诱导GD动物模型,以研究异常表达于GD患者甲状腺滤泡上皮细胞上的MHC-Ⅱ分子是否是GD的致病因素。方法试验组C57BL/6小鼠8只,用hM12细胞进行腹腔免疫,每2周1次,共6次,对照组C57BL/6小鼠5只,用M12细胞免疫,方法同试验组。受试小鼠末次免疫5周后,检测以下指标:甲状腺激素水平;甲状腺刺激性抗体(TSAb);甲状腺组织学检查。结果C57BL/6小鼠试验组2/8小鼠诱导为Graves甲亢。C57BL/6小鼠的T细胞(MHC-Ⅱ为H-2b)不能识别由hM12细胞(H-2d)提呈的抗原,C57BL/6小鼠出现GD样变化可能是hM12细胞表达的TSHR被小鼠体内职业性抗原递呈细胞(APCs)获取,经加工处理提呈给T细胞,诱发自身免疫反应的结果。结论异常表达于GD患者甲状腺滤泡上皮细胞上的MHC-Ⅱ分子可能与GD的发病无关,而是一种自身免疫反应的继发现象。更多还原

【Abstract】 Objective C57BL/6 mice(H-2b) were immunized with hM12 cells,which co-expressing major histocom-patibility complex(MHC) class Ⅱ molecules and human thyrotropin receptor(TSHR) molecules,to development animal model of Graves’ disease(GD) and to conjecture whether MHC class Ⅱ molecules expression by the human epithelial thyroid cell in GD would contribute to the pathogenesis of GD.Methods C57BL/6 mice in experimental groups(H-2b) were immunized i.p.per 2 weeks with hM12 cells for six times,while mice in control groups were immunized with M12 cell.Five weeks later,the thyroids were histologically examined,and serum samples were tested for thyroid-stimulating antibodies(TSAb) and thyroid hormone levels.Results Two C57BL/6 mice in experiment groups developed Graves’ disease change.T cells of C57BL/6 mice could not recognize the hTSHR presented by hM12 cells because of different H-2 molecules.hTSHR expressed by hM12 cells may be treated by professional APCs of C57BL/6 mice,then presented to T cells and induced Graves’ -like disease.Conclusion MHC class Ⅱ molecules expressed on human epithelial thyroid cell in GD might not be a pathogenic factor of GD,but a secondary phenomenon induced by other immune disturbance.更多还原