SPONTANEOUS DIABETES--PATHOGENESIS AND TREATMENT

主要的注意力集中在定义免疫的实验上。 BB大鼠自发性糖尿病的发病机制， 与人类疾病有许多共同特征。 因为我们发现， 移植的胰岛会受到自身免疫性损伤， 天然胰岛、胰岛移植物将被用作探针来研究 自身免疫性胰岛损伤中的MHC限制现象。 采用 近交系和同类系的大鼠将尝试定位 负责限制现象的MHC区域。 将研究抗原呈递细胞耗竭的胰岛移植物的命运 在免疫耐受宿主中鉴定和表征活性 参与胰岛损伤的效应细胞。 调查还 计划确定在这些耐受宿主中观察到的胰岛损伤是否 是由正常干细胞的异常分化引起的， 自身免疫环境，其导致这些宿主中的自身反应性细胞。 检查T细胞和MHC限制的胸腺教育的作用 致糖尿病效应细胞的模式是该基金的主要目标。 拟议研究中可能具有直接实际意义的方面 重要是：1）胰岛移植技术的完善; 2）标记物 糖尿病前期状态; 3）开发安全有效的 免疫抑制作为糖尿病治疗或预防。

Primary attention is focused on experiments to define the immune pathogenesis of spontaneous diabetes in the BB rat, an animal model with many features in common with the human disease. Since we have found that transplanted islets succumb to the same autoimmune damage which destroys the native islets, islet grafts will be employed as a probe to investigate the phenomenon of MHC restriction in autoimmune islet damage. Employing inbred and congenic strains of rats attempts will be made to locate the region of MHC responsible for restriction phenomena. The fate of antigen presenting cell depleted islet grafts will be studied in immunologically tolerant hosts to identify and characterize the activity of effector cells involved in islet damage. Investigations are also planned to determine whether the islet damage seen in these tolerant hosts is caused by an aberrant differentiation of normal stem cells in an autoimmune milieu which results in autoreactive cells in these hosts. Examination of the role of thymic education of T cells and MHC restriction patterns of diabetogenic effector cells is a major goal of the grant. Aspects of the proposed studies which are of possible immediate practical importance are: 1) perfection of islet transplant techniques; 2) markers for prediabetic states; 3) development of safe and effective immunosuppression as treatment or prophylaxis of diabetes.