Targeting CD8+ T Cells to Prevent b Cell Destruction

超出所提供的空间。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介导的朗格汉斯胰岛产生胰岛素的b细胞的破坏。糖尿病的治疗主要集中在胰岛素替代的使用上。然而，这种治疗方法很难规范，而且有许多缺点。虽然移植胰岛的外科技术已经触手可及，但问题依然存在。首先也是最重要的事实是，即使是同种移植物也会由于引起最初胰岛细胞损失的相同自身免疫机制而被排斥。必须控制这一过程，以促进有效的移植功能。迄今为止，对T1D发病机制和治疗的了解大多集中在CD4+ T细胞的作用上。在本提案中，我们将目前的免疫调节思想扩展到CD8+细胞在T1D中的作用。我们试图研究b细胞特异性CD8+ T细胞的库和调节，CD8+ T细胞亚群、Tcl和Tc2在调节中的作用，以及CD4+ T细胞产生的细胞因子在形成CD8+ T细胞反应中的作用。这将通过结合使用MHC I类四聚体、肽和新的免疫策略来实现。然后，我们将利用这些信息来偏离或激活/删除肽特异性T细胞，并控制T1D中关键的CD8+ T细胞反应，以实现有效的胰岛细胞移植。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. 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, this 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. Heretofore, most of the efforts in understanding the pathogenesis and treatment of T1D have focused on the role of CD4+ T cells. In this proposal we expand the current ideas of immunoregulation to CD8+ cells in T1D. We seek to study the repertoire and regulation of b cell specific CD8+ T cells, the role of CD8+ T cell subset, Tcl and Tc2 on regulation, and the roles of cytokines produced by CD4+ T cells in shaping the CD8+ T cell response. This will be accomplished by combing the use of MHC class I tetramers, peptides and novel immunization strategies. We will then use this information to deviate or anergize/delete peptide specific T cells and control the critical CD8+ T cell response in T1D to allow effective islet cell transplantation. PERFORMANCE SITE ========================================Section End===========================================