AUTOREATIVE T CELLS RESISTANT TO TOLERANCE IN DIABETES

这项提案长期目标是确定和描述 导致自身免疫性I型糖尿病的T细胞。通过 确定涉及的特定人群，更精确的干预 可以采用各种方法来预防这种疾病的发展。AS 已被确定为本年度所有项目的中心主题 建议，我们已经确定了细胞凋亡和自身免疫之间的联系 疾病。具体地说，我们从我们对易患糖尿病的BB- DP大鼠自身反应性T细胞抵抗凋亡和 无能诱导，它们最好的特征是髓质胸腺细胞 而不是成熟的外周T细胞。我们的工作假设是 耐药表型与这些胸腺细胞 逃避正常的选择过程，即删除自身反应性T细胞 胸腺。这种对无能和细胞凋亡的抵抗是至关重要的 一种自身反应性“髓质胸腺细胞”亚群的特性 自身免疫性糖尿病的发展。这项建议的具体目的 将侧重于糖尿病易感基因对 自身反应性T细胞的特性及其测定 如果能从糖尿病患者的胸腺中分离出自身反应性T细胞 容易患糖尿病和非糖尿病的动物。

The long term objective of this proposal is to identify and characterize the T cells responsible for causing autoimmune type I diabetes. By identifying the specific populations involved, more precise intervention approaches can be employed to prevent the development of the disease. As has been determined to be a central theme of all projects in this proposal, we have identified a link between apoptosis and autoimmune disease. Specifically, we conclude from our studies of diabetes prone BB- DP rats that the autoreactive T cells are resistant to apoptosis and anergy induction and they are best characterized as medullary thymocytes rather than mature peripheral T cells. Our working hypothesis is that the resistant phenotype is associated with the way in which these thymocytes escape the normal selection process that deletes self reactive T cells in the thymus. This resistance to anergy and apoptosis is a critical characteristic of an autoreactive "medullary thymocyte" subset involved in the development of autoimmune diabetes. The specific aims of this proposal will focus on the genetic contribution of diabetes susceptibility genes to the characteristics ascribed to the autoreactive T cells and determining if the autoreactive T cells can be isolated from the thymus of diabetes prone and non diabetic animals.