Targeting CD8+ T Cell to Prevent B Cell Destruction

1型糖尿病(T1-D)是一种组织特异性自身免疫性疾病，其特征是T细胞介导的 朗格汉斯胰岛分泌胰岛素的b细胞。糖尿病的治疗主要集中在使用 胰岛素替代疗法。然而，这种治疗方法可能很难监管，而且有许多缺点。而当 移植胰岛的外科技术现在近在咫尺，但问题仍然存在。首先也是最重要的 事实是，即使是同基因移植物也会被排斥，这是因为导致 最初的胰岛细胞丢失。这一过程必须加以控制，以促进有效的移植功能。这项提议将 使用两种新方法来清除自身抗原反应性T细胞。我们将使用基于MHC-四聚体的结构 装载了自身的多肽，并与植物毒素Saporin结合。我们将使用毒素包裹的四聚体来 删除自身反应性T细胞。这种方法将在体外和体内得到验证。我们还将改编一个新的 针对特定T细胞的一类纳米粒子，Print(在非湿润模板中进行粒子复制) 通过MHC包衣和携带抗菌药物。抗体靶向与药物选择性的结合 将在针对自身免疫方面提供一个新的效率水平。

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.