The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in nonobese diabetic mice at different ages
The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in nonobese diabetic mice at different ages
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DOI：
10.3109/08916934.2010.548839
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发表时间：
2011-09-01
期刊：
影响因子：
3.5
通讯作者：
Abiru, Norio
中科院分区：
文献类型：
--
作者：
Nakahara, Mami;Nagayama, Yuji;Abiru, Norio
非肥胖糖尿病（NOD）小鼠自发地发展几种自身免疫性疾病，包括1型糖尿病和较小程度的甲状腺炎和甲状腺炎。效应性T细胞（Tefs）和调节性T细胞（Tregs）之间的不平衡最近被认为是NOD小鼠疾病发病机制的一个机制，但以前的研究表明，不同的Treg耗竭时间和方法会产生不同的结果。因此，本研究旨在比较通过相同方法（抗CD 25抗体）消除Treg对不同年龄NOD小鼠器官特异性自身免疫性疾病谱的影响。在10日龄时通过抗CD 25抗体进行的Treg耗竭加速了我们检查的所有三种疾病（胰岛炎/糖尿病、甲状腺炎和甲状腺炎）的发展;在4周龄时Treg耗竭仅加速了糖尿病，但不加速甲状腺炎或甲状腺炎;在12周龄时Treg耗竭仅加速了甲状腺炎的发展，对糖尿病或甲状腺炎的影响很小。然而，在10日龄时TdR耗尽的小鼠中观察到胰岛素自身抗体（IAA）水平升高，而在4周时则未观察到。因此，Treg耗竭对器官特异性自身免疫性疾病谱的影响取决于NOD小鼠中抗CD 25抗体注射的时机。随着年龄的增长，糖尿病患者的Teffs和Tglutamine之间的平衡逐渐向Teffs主导的方向倾斜，但甲状腺炎和甲状腺炎患者的这种平衡可能会发生更复杂的变化。我们的数据还表明，IAA的水平不一定与糖尿病的发展相关。
The nonobese diabetic (NOD) mouse spontaneously develops several autoimmune diseases, including type 1 diabetes and to a lesser extent thyroiditis and sialitis. Imbalance between effector T cells (Teffs) and regulatory T cells (Tregs) has recently been proposed as a mechanism for the disease pathogenesis in NOD mice, but previous studies have shown the various outcomes by different timing and methods of Treg-depletion. This study was, therefore, designed to compare the consequences of Treg-depletion by the same method (anti-CD25 antibody) on the spectrum of organ-specific autoimmune diseases in NOD mice of different ages. Treg-depletion by anti-CD25 antibody at 10 days of age accelerated development of all three diseases we examined (insulitis/diabetes, thyroiditis, and sialitis); Treg-depletion at 4 weeks of age accelerated only diabetes but not thyroiditis or sialitis; and Treg-depletion at 12 weeks of age hastened only development of thyroiditis and exhibited little influence on diabetes or sialitis. Increased levels of insulin autoantibodies (IAA) were, however, observed in mice depleted of Tregs at 10 days of age, not in those at 4 weeks. Thus, the consequences of Treg-depletion on the spectrum of organ-specific autoimmune diseases depend on the timing of anti-CD25 antibody injection in NOD mice. Aging gradually tips balance between Teffs and Tregs toward Teff-dominance for diabetes, but this balance for thyroiditis and sialitis likely alters more intricately. Our data also suggest that the levels of IAA are not necessarily correlated with diabetes development.