Is lack of peripheral tolerance induction a cause for diabetes in the nonobese diabetic mouse?

Lund, Torben and Strid, Jessica (2000) Is lack of peripheral tolerance induction a cause for diabetes in the nonobese diabetic mouse? Archivum Immunologiae et Therapiae Experimentalis, 48 (5) . pp. 405-416. ISSN 1661-4917 [Article]


The nonobese diabetic (NOD) mouse is a spontaneous animal model for type 1 diabetes characterized by a selective destruction of the insulin producing b-cells in the pancreas. As in humans, the disease is controlled by several susceptibility genes some of which maps to the major histocompatibility complex on chromosome 17. However environmental factors contributes also 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 that produce Th2 cells. In addition to activate na?ve 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 development of peripheral tolerance than DC1 cells. Further to abnormalities in development of bone marrow-derived antigen presenting cells, the NOD mouse has also 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 subset of dendritic cells with a skewing towards DC1 cells; thus having a reduced ability to generate peripheral tolerance to a number of autoantigens.

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 3976
Depositing User: Mrs Sue Black
Date Deposited: 04 Feb 2010 15:21
Last Modified: 13 Oct 2016 14:17

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