Prabakar Kamalaveni R, Pugliese Alberto
Immunogenetics Program, Diabetes Research Institute, University of Miami School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USA.
Curr Diab Rep. 2004 Apr;4(2):101-7. doi: 10.1007/s11892-004-0064-y.
Studies in both humans and rodent models provide new insight into key mechanisms regulating tolerance to self-molecules. There is evidence that tissue-specific molecules are expressed in the thymus and peripheral lymphoid tissues (PLTs) by specialized antigen-presenting cells (APCs), and that such expression is critical for self-tolerance. Insulin, a key hormone exclusively produced by pancreatic beta cells and a critical autoantigen in type 1 diabetes, provides an excellent example of a molecule with tissue-restricted expression that is ectopically expressed by APCs in both thymus and PLTs. APCs may play a role in insulin presentation in both the central and peripheral immune system. Functional data from several transgenic and knockout mouse models, some specific for the expression of insulin, help dissect the significance of self-molecule presentation by APCs and its role in autoimmune diabetes.
对人类和啮齿动物模型的研究为调节对自身分子耐受性的关键机制提供了新的见解。有证据表明，组织特异性分子由专门的抗原呈递细胞（APC）在胸腺和外周淋巴组织（PLT）中表达，并且这种表达对于自身耐受性至关重要。胰岛素是胰腺β细胞唯一产生的关键激素，也是1型糖尿病中的关键自身抗原，它是一种组织限制性表达分子的极佳例子，该分子在胸腺和PLT中均由APC异位表达。APC可能在中枢和外周免疫系统的胰岛素呈递中发挥作用。来自几种转基因和基因敲除小鼠模型（其中一些对胰岛素表达具有特异性）的功能数据有助于剖析APC呈递自身分子的意义及其在自身免疫性糖尿病中的作用。
