Coexpression of susceptible and resistant HLA class II transgenes in murine experimental autoimmune thyroiditis: DQ8 molecules downregulate DR3-mediated thyroiditis.
Coexpression of susceptible and resistant HLA class II transgenes in murine experimental autoimmune thyroiditis: DQ8 molecules downregulate DR3-mediated thyroiditis.
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小鼠实验性自身免疫性甲状腺炎中易感和耐药 HLA II 类转基因的共表达：DQ8 分子下调 DR3 介导的甲状腺炎。
DOI：
10.1006/jaut.2002.0587
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发表时间：
2002
影响因子：
12.8
通讯作者：
Kong,Yi-chiM
中科院分区：
文献类型：
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作者：
Flynn,JeffreyC;Wan,Qiang;Panos,JohnC;McCormick,DanielJ;Giraldo,AlvaroA;David,ChellaS;Kong,Yi-chiM
用自身抗原甲状腺球蛋白（Tg）免疫遗传易感小鼠可诱发实验性自身免疫性甲状腺炎（EAT）。由于易感性与H2 II类分子有关，我们已经产生了人类白细胞抗原（HLA）II类转基因小鼠，以研究潜在的HLA与桥本甲状腺炎的关联。将DR 3（HLA-DR/DRB 1 *0301）和DQ 8（HLA-DQA 1 *0301/DQB 1 *0302）转基因导入II类阴性的Ab 0/B10和Ab 0非肥胖糖尿病（Ab 0/NOD）小鼠。先前的工作表明，DR 3转基因小鼠对小鼠Tg和人Tg诱导的EAT均敏感，而DQ 8转基因小鼠仅对人Tg诱导中度敏感。在这份报告中，我们研究了DQ 8转基因对小鼠Tg和人Tg诱导的EAT在双转基因DR 3/DQ 8小鼠的影响。在小鼠Tg诱导后，DR 3 + DQ 8 + Ab 0/B10小鼠中的甲状腺炎的严重程度显著低于DR 3+小鼠，但比DQ 8+小鼠更严重。在另一个背景品系Ab 0/NOD中，在DR 3+和DR 3 + DQ 8+小鼠之间未观察到甲状腺炎差异。然而，与DR 3+小鼠相比，用人Tg免疫后，DQ 8共表达下调了甲状腺炎的严重程度，而甲状腺炎比DQ 8+小鼠更广泛。因此，根据背景菌株和用于诱导疾病的Tg，DQ 8转基因的存在可以减少DR 3分子介导的甲状腺炎。
Experimental autoimmune thyroiditis (EAT) can be induced in genetically susceptible mice by immunization with the self antigen, thyroglobulin (Tg). Since susceptibility is linked to H2 class II molecules, we have generated human leukocyte antigen (HLA) class II transgenic mice to study potential HLA associations with Hashimoto's thyroiditis. DR3 (HLA-DRA/DRB1*0301) and DQ8 (HLA-DQA1*0301/DQB1*0302) transgenes were introduced into class II-negative Ab0/B10 and Ab0nonobese diabetic (Ab0/NOD) mice. Previous work had shown that DR3 transgenic mice were susceptible to both mouse Tg and human Tg-induced EAT, whereas DQ8 transgenic mice were moderately susceptible only to human Tg induction. In this report, we examined the effect of DQ8 transgene on mouse Tg- and human Tg-induced EAT in double transgenic DR3/DQ8 mice. After mouse Tg induction, thyroiditis in DR3+DQ8+Ab0/B10 mice was significantly less severe than in DR3+mice but more severe than in DQ8+mice. No difference in thyroiditis was observed between DR3+and DR3+DQ8+mice in another background strain, Ab0/NOD. However, after immunization with human Tg, DQ8 coexpression downregulated thyroiditis severity, compared to DR3+mice, whereas thyroiditis was more extensive than in DQ8+mice. Thus, depending on the background strain and the Tg used to induce disease, the presence of the DQ8 transgene can reduce thyroiditis mediated by DR3 molecules.