Lund T, Strid J
Department of Immunology and Molecular Pathology, Windeyer Institute for Medical Sciences, University College London, UK.
Arch Immunol Ther Exp (Warsz). 2000;48(5):405-16.
The non-obese diabetic (NOD) mouse is a spontaneous animal model for type 1 diabetes characterized by a selective destruction of the insulin producing beta cells in the pancreas. As in humans, the disease is controlled by several susceptibility genes, some of which map to the major histocompatibility complex on chromosome 17. However, environmental factors also contribute to the development of the disease in the NOD mouse, presumably through controlling the balance between the Th1 and Th2 response in the animal. Recent observations have shown that the NOD mouse has abnormalities in the development of bone marrow-derived antigen-presenting cells. These include the most potent activators of naive T cells, the dendritic cells, which exist in at least two different sub-populations; DC1 cells, responsible for activation of Th1 cells, and DC2 cells, which produce Th2 cells. In addition to activating naive T cells, the dendritic cells are also involved in generating central and peripheral tolerance to self molecules. In this process DC2 cells appear to be more important for the development of peripheral tolerance than DC1 cells. Besides abnormalities in the development of bone marrow-derived antigen-presenting cells, the NOD mouse also has a defect in the thymic selection of T cells, leading to a higher concentration of autoreactive T cells. We speculate that the NOD mouse may develop an imbalance in the two subsets of dendritic cells with a skewing towards DC cells, thus having a reduced ability to generate peripheral tolerance to a number of autoantigens.
非肥胖型糖尿病（NOD）小鼠是1型糖尿病的自发动物模型，其特征是胰腺中产生胰岛素的β细胞被选择性破坏。与人类一样，该疾病由多个易感基因控制，其中一些基因定位于17号染色体上的主要组织相容性复合体。然而，环境因素也会促使NOD小鼠发病，可能是通过控制动物体内Th1和Th2反应之间的平衡来实现的。最近的观察结果表明，NOD小鼠骨髓来源的抗原呈递细胞发育异常。这些细胞包括幼稚T细胞的最强激活剂——树突状细胞，其至少存在两种不同的亚群；负责激活Th1细胞的DC1细胞和产生Th2细胞的DC2细胞。除了激活幼稚T细胞外，树突状细胞还参与对自身分子产生中枢和外周耐受性。在此过程中，DC2细胞似乎比DC1细胞在外周耐受性的发展中更为重要。除了骨髓来源的抗原呈递细胞发育异常外，NOD小鼠在胸腺T细胞选择方面也存在缺陷，导致自身反应性T细胞浓度升高。我们推测，NOD小鼠可能会出现两种树突状细胞亚群失衡，偏向DC细胞，从而降低对多种自身抗原产生外周耐受性的能力。
