Targeting CD8+ T Cell to Prevent B Cell Destruction

1型糖尿病（TlD）是一种组织特异性自身免疫性疾病，其特征在于T介导的对糖尿病细胞的破坏。 胰岛的产生胰岛素的B细胞。糖尿病的治疗集中在使用 胰岛素替代然而，这种治疗可能难以规范并且具有许多缺点。而 胰岛移植的外科技术已经成熟，但问题仍然存在。首先 事实上，即使是同系移植物也会由于引起移植物排斥的相同自身免疫机制而被排斥， 最初的胰岛细胞丢失。这个过程必须加以控制，以促进有效的移植功能。这项建议会 使用两种新方法去除自身抗原反应性T细胞。我们将使用基于MHC-四聚体的构建体 装载有自身肽并与植物毒素皂草素偶联。我们将使用毒素包被的四聚体， 删除自身反应性T细胞。该方法将在体外和体内进行验证。我们还将采用新的 一类纳米颗粒，PRINT（非湿润模板中的颗粒复制），靶向特定T细胞 并携带免疫抑制药物。抗体靶向与药物选择性的结合 将为靶向自身免疫提供新的效率水平。

Type 1 diabetes (T1 D) is a tissue specific autoimmune disease characterized by the T mediated destruction of the insulin producing b cells of the islets of Langerhans. Treatment of diabetes has focused on the use of insulin replacement. However, th is treatment can be difficult to regulate and has many shortcomings. While the surgical techniques for transplanting pancreatic islets is now at hand, problems remain. First and foremost is that fact that even syngeneic grafts are rejected due to the same autoimmune mechanisms that caused the initial islet cell loss. This process must be controlled to promote effective transplant function. This proposal will use two new approaches to remove autoantigen reactive T cells. We will use MHC-tetramer based constructs loaded with self peptides and coupled with the plant toxin, saporin. We will use the toxin coated tetramers to delete self-reactive T cell. This approach will be validated in vitro and them in vivo. We will also adapt a new class of nanoparticles, PRINT (Particle Replication in Non-wetting Templates) to be targeted to specific T cells by MHC coating and to carry Iymphotoxic drugs. The combination of targeting by antibody and drug selectivity will provide a new level of efficiency in targeting to autoimmunity.