You Sylvaine, Chatenoud Lucienne
INSERM U1151, Hôpital Necker-Enfants Malades, 149 Rue de Sevres, 75015, Paris, France.
CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
Methods Mol Biol. 2016;1371:117-42. doi: 10.1007/978-1-4939-3139-2_8.
Type 1 diabetes (T1D) results from a chronic and selective destruction of insulin-secreting β-cells within the islets of Langerhans of the pancreas by autoreactive CD4(+) and CD8(+) T lymphocytes. The use of animal models of T1D was instrumental for deciphering the steps of the autoimmune process leading to T1D. The non-obese diabetic (NOD) mouse and the bio-breeding (BB) rat spontaneously develop the disease similar to the human pathology in terms of the immune responses triggering autoimmune diabetes and of the genetic and environmental factors influencing disease susceptibility. The generation of genetically modified models allowed refining our understanding of the etiology and the pathogenesis of the disease. In the present review, we provide an overview of the experimental models generated and used to gain knowledge on the molecular and cellular mechanisms underlying the breakdown of self-tolerance in T1D and the progression of the autoimmune response. Immunotherapeutic interventions designed in these animal models and translated into the clinical arena in T1D patients will also be discussed.
1型糖尿病(T1D)是由自身反应性CD4(+)和CD8(+) T淋巴细胞对胰腺胰岛内胰岛素分泌β细胞进行慢性和选择性破坏所致。T1D动物模型的使用对于解读导致T1D的自身免疫过程的各个步骤至关重要。非肥胖糖尿病(NOD)小鼠和生物繁殖(BB)大鼠在引发自身免疫性糖尿病的免疫反应以及影响疾病易感性的遗传和环境因素方面,会自发发展出与人类病理相似的疾病。转基因模型的产生使我们对该疾病的病因和发病机制有了更深入的了解。在本综述中,我们概述了为了解T1D中自身耐受性破坏和自身免疫反应进展的分子和细胞机制而构建和使用的实验模型。还将讨论在这些动物模型中设计并转化应用于T1D患者临床领域的免疫治疗干预措施。