MHC-LINKED PROTECTION FROM DIABETES DISSOCIATED FROM CLONAL DELETION OF T-CELLS
MHC-LINKED PROTECTION FROM DIABETES DISSOCIATED FROM CLONAL DELETION OF T-CELLS
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DOI：
10.1126/science.2115690
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发表时间：
1990-07-20
期刊：
影响因子：
56.9
通讯作者：
MATHIS, D
中科院分区：
文献类型：
--
作者：
BOHME, J;SCHUHBAUR, B;MATHIS, D
主要组织相容性复合体(MHC)的I-E分子可以预防非肥胖糖尿病(NOD)小鼠糖尿病的自发发展。通过在NOD遗传背景上培育野生型和启动子突变的E.alpha.k转基因来研究这种保护的机制。携带各种突变转基因的动物在不同的免疫活性细胞亚群上表达I-E，因此可以识别对I-E保护作用重要的细胞。尽管野生型转基因阻止了淋巴细胞向胰岛的渗透，但突变体中没有一个做到了这一点。然而，所有转基因都可以介导胸腺内携带识别I-E的可变区抗原受体的T细胞的清除。因此，I-E分子并不是简单地通过诱导自身反应性T细胞的删除来保护NOD小鼠免受糖尿病的影响。
The I-E molecule of the major histocompatibility complex (MHC) can prevent the spontaneous development of diabetes in nonobese diabetic (NOD) mice. The mechanism of this protection has been investigated by breeding wild-type and promoter-mutated E.alpha.k transgenes onto the NOD genetic background. Animals carrying the various mutated transgenes expressed I-E on different subsets of immunocompetent cells, and thus cells important for the I-E protective effect could be identifed. Although the wild-type transgene prevented the infiltration of lymphocytes into pancreatic islets, none of the mutants did. However, all of the transgenes could mediate the intrathymic elimination of T cells bearing antigen receptors with variable regions that recognize I-E. Thus, the I-E molecule does not protect NOD mice from diabetes simply by inducing the deletion of self-reactive T cells.