Studies on the poathogenesis of Graves' disease and new treatment using our recently established mouse model.

(1)遗传背景对Graves甲亢发生的影响：我们在小鼠模型中发现，非MHC基因而非MHC基因在Graves甲亢发生中起主要作用。(2)环境因素的影响：两者都不是环境因素。微生物而不是细菌/酵母成分似乎与疾病的发病机制有关。(3) Th1/Th2平衡对抗tsh受体免疫应答的影响：联合注射表达白细胞介素-4的腺病毒、感染曼氏血吸虫或服用a-半乳糖苷可预防Graves病诱导。然而，抗tshr免疫反应一旦被激活，th2免疫极化对病程影响不大，表明这种类型的免疫操作可能只是预防，而不是治疗。(4) TSH受体表位分析：TSH受体胞外结构域的n端是主要的表位，抗TSH受体抗体识别构象或线性表位。(5) B细胞缺失的影响：正常B细胞存在。对于抗tsh受体记忆T淋巴细胞的建立至关重要。

(1)The effect of genetic background on development of Graves' hyperthyroidism : we found that non-MHC genes, but not MHC, play a major role in development of Graves' hyperthyroidism in our mouse model.(2)The effect of environmental factors : Neither environmental. microorganisms nor bacterial/yeast components appear to be involved in the pathogenesis of disease.(3)The effect of Th1/Th2 balance of anti-TSH receptor immune response: Th2-immune deviation at the time of antigen-presentation by co-injection of adenovirus expressing interleukin-4, Schistosoma mansoni infection or administration of a-galactosylceremaide prevent Graves' disease induction. However, anti-TSHR immune response is once activated, Th2-immune polarization has little effect on disease course, indicating this type of immune manipulation may be just preventive, not therapeutic.(4)Analysis of the epitopes on TSH receptor : N-terminus of TSH receptor extracellular domain is the major epitopes, for anti-TSH receptor antibodies recognizing conformational or linear epitopes.(5)The effect of B cell deletion : Existence of normal B cell. population is essential for establishment of anti-TSH receptor memory T lymphocytes.