Targeting CD8+ T Cells 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，其特征在于T细胞介导的糖尿病性糖尿病。 破坏胰岛的胰岛素产生B细胞。糖尿病的治疗 重点关注胰岛素替代疗法的使用。然而，这种治疗可能难以规范， 有很多缺点。虽然移植胰岛的外科技术现在在 一方面，问题依然存在。首先也是最重要的是，即使是同基因移植也会因 导致最初胰岛细胞丧失的自身免疫机制。上述操作 控制以促进有效的移植功能。因此，大多数的努力在了解 T1 D的发病机制和治疗集中于CD 4 + T细胞的作用。本提案中 我们将目前的免疫调节思路扩展到T1 D中的CD 8+细胞。我们寻求研究 B细胞特异性CD 8 + T细胞的库和调节，CD 8 + T细胞亚群的作用，Tcl和 Tc 2对CD 4 + T细胞的调节作用，以及CD 4 + T细胞产生的细胞因子在CD 8 + T细胞形成中的作用 反应这将通过结合使用MHC I类四聚体、肽和多肽来实现。 新的免疫策略。然后，我们将使用此信息偏离或anergize/删除 肽特异性T细胞，并控制T1 D中的关键CD 8 + T细胞应答， 细胞移植

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.