SPONTANEOUS DIABETES--PATHOGENESIS AND TREATMENT

自发性糖尿病——发病机制和治疗

• 批准号: 3483464
• 负责人: CLYDE F BARKER
• 金额: $ 28.45万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-06-01 至 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3483464
• 关键词: T lymphocyte; autoimmune disorder; bone marrow transplantation; disease /disorder model; dissection; genetic strain; graft versus host disease; immunodeficiency; immunogenetics; mature animal; mixed lymphocyte reaction test; monoclonal antibody; newborn animals; pancreatic islet transplantation; serology /serodiagnosis; tissue /cell culture

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.

主要的注意力集中在定义免疫的实验上 大鼠自发性糖尿病发病机制的实验研究 与人类疾病有许多共同之处。因为我们已经发现 移植的胰岛会屈服于同样的自身免疫损伤，这会破坏 将以原生胰岛、胰岛移植物为探针进行研究 自身免疫性胰岛损伤中的MHC限制现象。用人 近交系和同源品系的老鼠将试图定位 负责限制现象的MHC区域。 抗原提呈细胞耗尽的胰岛移植物的命运将被研究。 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。调查也在进行中 计划确定这些耐受性宿主的胰岛损伤是否 是由正常干细胞的异常分化引起的 在这些宿主中产生自身反应细胞的自身免疫环境。 胸腺教育对T细胞的作用及其对MHC的限制 糖尿病效应细胞的模式是赠款的一个主要目标。 拟议研究中可能立即具有实际意义的方面 重要的是：1)完善胰岛移植技术；2)标记 用于糖尿病前期状态；3)开发安全有效的 免疫抑制作为糖尿病的治疗或预防。