Depletion of CD4+CD25+ regulatory T cells exacerbates sodium iodide-induced experimental autoimmune thyroiditis in human leucocyte antigen DR3 (DRB1*0301) transgenic class II-knock-out non-obese diabetic mice
Depletion of CD4+CD25+ regulatory T cells exacerbates sodium iodide-induced experimental autoimmune thyroiditis in human leucocyte antigen DR3 (DRB1*0301) transgenic class II-knock-out non-obese diabetic mice
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DOI：
10.1111/j.1365-2249.2006.03303.x
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发表时间：
2007-03-01
影响因子：
4.6
通讯作者：
Kong，Y. M.
中科院分区：
文献类型：
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作者：
Flynn，J. C.;Meroueh，C.;Kong，Y. M.
遗传和环境因素都有助于自身免疫性疾病的发展。以前，我们评估了遗传因素在桥本甲状腺炎（HT）的人源化小鼠模型，通过免疫人类白细胞抗原DR 3（HLA-DR 3）和HLA-DQ 8转基因II类基因敲除非肥胖糖尿病（NOD）小鼠。DR 3+小鼠对小鼠甲状腺球蛋白（mTg）和人（h）Tg诱导的实验性自身免疫性甲状腺炎（EAT）敏感，而DQ 8+小鼠仅对hTg敏感。由于一个与HT相关的环境因素，并在非转基因模型中进行了测试，即碘化钠（NaI）摄入量增加，我们检查了DR 3+和/或DQ 8+小鼠对NaI诱导疾病的易感性。小鼠在饮用水中用NaI处理8周。 在0.05%NaI下，23%的DR 3+、0%的DQ 8+和20%的DR 3 + DQ 8+小鼠有甲状腺破坏。未观察到脾细胞增殖至mTg。大多数小鼠检测不到抗mTg抗体，但抗体水平低的小鼠通常患有甲状腺炎。在0.3%NaI下，较高百分比的DR 3+和DR 3 + DQ 8+小鼠发生破坏性甲状腺炎，但无统计学显著性。然而，当DR 3+小鼠在NaI治疗之前已经耗尽了CD 4 + CD 25+调节性T细胞时，破坏性甲状腺炎（68%）和血清抗mTg抗体进一步恶化。DQ 8分子的存在不会改变DR 3 + DQ 8+小鼠对碘化钠诱导的甲状腺炎的易感性，这与mTg诱导的EAT的早期发现相似。DR 3+小鼠对NaI诱导的EAT的易感性，在存在和不存在调节性T细胞的情况下，证明了HLA II类转基因小鼠在评估自身免疫性甲状腺疾病中环境因素和免疫失调的作用中的有用性。
Both genetic and environmental factors contribute to autoimmune disease development. Previously, we evaluated genetic factors in a humanized mouse model of Hashimoto's thyroiditis (HT) by immunizing human leucocyte antigen DR3 (HLA-DR3) and HLA-DQ8 transgenic class II-knock-out non-obese diabetic (NOD) mice. DR3+mice were susceptible to experimental autoimmune thyroiditis (EAT) induction by both mouse thyroglobulin (mTg) and human (h) Tg, while DQ8+mice were weakly susceptible only to hTg. As one environmental factor associated with HT and tested in non-transgenic models is increased sodium iodide (NaI) intake, we examined the susceptibility of DR3+and/or DQ8+mice to NaI-induced disease. Mice were treated for 8 weeks with NaI in the drinking water. At 0·05% NaI, 23% of DR3+, 0% of DQ8+and 20% of DR3+DQ8+mice had thyroid destruction. No spleen cell proliferation to mTg was observed. Most mice had undetectable anti-mTg antibodies, but those with low antibody levels usually had thyroiditis. At 0·3% NaI, a higher percentage of DR3+and DR3+DQ8+mice developed destructive thyroiditis, but it was not statistically significant. However, when DR3+mice had been depleted of CD4+CD25+regulatory T cells prior to NaI treatment, destructive thyroiditis (68%) and serum anti-mTg antibodies were exacerbated further. The presence of DQ8 molecules does not alter the susceptibility of DR3+DQ8+mice to NaI-induced thyroiditis, similar to earlier findings with mTg-induced EAT. Susceptibility of DR3+mice to NaI-induced EAT, in both the presence and absence of regulatory T cells, demonstrates the usefulness of HLA class II transgenic mice in evaluating the roles of environmental factors and immune dysregulation in autoimmune thyroid disease.