André I, Gonzalez A, Wang B, Katz J, Benoist C, Mathis D
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, Strasbourg, France.
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2260-3. doi: 10.1073/pnas.93.6.2260.
In the last few years, data from experiments employing transgenic models of autoimmune disease have strengthened a particular concept of autoimmunity: disease results not so much from cracks in tolerance induction systems, leading to the generation of anti-self repertoire, as from the breakdown of secondary systems that keep these cells in check. T cells with anti-self specificities are readily found in disease-free individuals but ignore target tissues. This is also the case in some transgenic models, in spite of overwhelming numbers of autoreactive cells. In other instances, local infiltration and inflammation result, but they are well tolerated for long periods of time and do not terminally destroy target tissue. We review the possible molecular and cellular mechanisms that underlie these situations, with a particular emphasis on the destruction of pancreatic beta cells in transgenic models of insulin-dependent disease.
在过去几年中，利用自身免疫性疾病转基因模型进行实验所获得的数据强化了一种特定的自身免疫概念：疾病与其说是由于耐受性诱导系统出现缺陷从而导致产生抗自身抗体库，不如说是由于维持这些细胞平衡的二级系统发生故障所致。具有抗自身特异性的T细胞在无病个体中很容易被发现，但它们会忽略靶组织。在一些转基因模型中也是如此，尽管存在大量的自身反应性细胞。在其他情况下，会出现局部浸润和炎症，但它们在很长一段时间内都能被很好地耐受，不会最终破坏靶组织。我们回顾了这些情况背后可能的分子和细胞机制，特别强调了胰岛素依赖型疾病转基因模型中胰腺β细胞的破坏。
