PREVENTION OF AUTOIMMUNE INSULITIS BY EXPRESSION OF I-E MOLECULES IN NOD MICE
PREVENTION OF AUTOIMMUNE INSULITIS BY EXPRESSION OF I-E MOLECULES IN NOD MICE
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DOI：
10.1038/328432a0
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发表时间：
1987-07-30
期刊：
影响因子：
64.8
通讯作者：
KISHIMOTO, T
中科院分区：
文献类型：
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作者：
NISHIMOTO, H;KIKUTANI, H;KISHIMOTO, T
NOD(非肥胖糖尿病)小鼠自发发展为胰岛素依赖型糖尿病(IDDM)，以自身免疫性胰岛素炎为特征，涉及胰岛周围和胰岛内的淋巴细胞渗透，随后胰岛β(β)细胞破坏1-5，类似于人类IDDM6，7。在NOD和C57BL/6小鼠之间的育种研究中的遗传分析表明，独立染色体上的两个隐性基因有助于胰岛素依赖症的发展8。两个隐性致糖尿病基因中的一个被发现与主要组织相容性复合体(MHC)9连锁。这是有趣的，因为NOD株有一个独特的II类MHC：它不表达I-E分子，因为在Northern印迹分析中看不到I-E a链的信使RNA；I-A分子不能被任何可用的单抗或同种或自身反应性T细胞克隆检测到，尽管它们的表达是由传统的抗Ia抗原9的抗血清控制的。为了研究II类MHC分子的异常表达是否可能与自身免疫性胰腺炎的发生有关，我们试图通过使用表达I-E的C57BL/6(B6(Eαd))转基因小鼠10来选择性地表达I-E分子，而不在17号染色体上引入其他基因。我们在这里报道，在NOD小鼠中I-E分子的表达可以预防自身免疫性胰岛素炎的发展。
The NOD (non-obese diabetic) mouse spontaneously develops insulin-dependent diabetes mellitus (IDDM) characterized by autoimmune insulitis, involving lymphocytic infiltration around and into the islets followed by pancreatic beta (β) cell destruction1–5, similar to human IDDM6,7. Genetic analysis in breeding studies between NOD and C57BL/6 mice has demonstrated that two recessive genes on independent chromosomes contribute to the development of insulitis8. One of the two recessive diabetogenic genes was found to be linked to the major histocompatibility complex (MHC)9. This is of interest, because the NOD strain has a unique class II MHC: it does not express I–E molecules as no messenger RNA for the a-chain of I–E is visible in Northern blot analysis; I–A molecules are not detected with any available monoclonal antibodies or by allo-reactive or autoreactive T-cell clones, although their expression is domonstrated with a conventional antiserum to Ia antigens9. To examine whether the unusual expression of class II MHC molecules may be responsible for the development of autoimmune insultitis, we attempted to express I–E molecules in NOD mice selectively, without introducing other genes on chromosome 17 by using I–E-expressing C57BL/6 (B6(Eαd)) transgenic mice10. We report here that the expression of I–E molecules in NOD mice can prevent the development of autoimmune insulitis.