Regulation of Ocular Tolerance by Gamma/delta T Cells

描述(申请人提供)：眼睛是一种免疫特权 移植组织存活时间远长于传统部位的部位， 比如皮肤。此外，细胞抗原和可溶性抗原都被放置在 眼球前房引起一种全身性的耐受，称为ACAID， 其中延迟性超敏反应和补体固定抗体对 一种免疫原型的抗原被抑制。我们最近的研究 证明了诱导细胞溶解T细胞反应也是深刻的 在接受眼部抗原的小鼠中被抑制。我们的数据还表明，眼睛 在缺乏γ/Delta T细胞的小鼠中不会诱导耐受 正常小鼠脾γ/Delta T细胞过继转移的研究 重构了宽容。 拟议研究的长期目标是通过以下方式确定机制 在CD4和CD8中，哪些Gamma/Delta T细胞调节眼睛耐受性 T细胞反应。我们将检验ACAID诱导 抗原提呈细胞和NKα/βT细胞是 脾内伽马/德尔塔T细胞活化。第二个目标是测试 假设在ACAID中激活的伽马/德尔塔T细胞是抗原特异性的， 调节性T细胞。我们将确定伽马/德尔塔T细胞是否会诱导CD8， α/βTCR在ACAID中成为传出抑制T细胞无论是 伽马/增量T细胞(和/或CD8抑制效应T细胞)表达记忆 将使用PLAP/Cre转基因B6小鼠进行功能评估。最后，一个新的 使用ROSA26R TG小鼠的模型将被用来检验ACAID的假设 诱导APC可在体内识别和示踪。 了解ACAID的机制有朝一日可能被用来预防移植物 拒绝。先前被激发的个体的免疫反应可被抑制 ACAID。因此，了解ACAID也可能提供新的治疗方法 自身免疫性疾病患者出现症状后。

DESCRIPTION (provided by applicant): The eye is an immunologically privileged site where transplanted tissues survive much longer than in conventional sites, such as the skin. Moreover, both cellular and soluble antigens placed in the anterior chamber of the eye induce a systemic form of tolerance, called ACAID, in which delayed hypersensitivity and complement fixing antibody responses to an immunogenic form of the antigen are inhibited. Our recent studies demonstrate that the induction of cytolytic T cell responses is also profoundly suppressed in mice receiving ocular antigens. Our data also show that ocular tolerance is not induced in mice that are depleted of gamma/delta T cells and the adoptive transfer of splenic gamma/delta T cells from normal mice reconstitutes tolerance. The long-term goal of the proposed studies is to determine the mechanisms by which gamma/delta T cells regulate ocular tolerance as manifest in CD4 and CD8 T cell responses. We will test the hypothesis that ACAID inducing antigen-presenting cells and NK alpha/beta T cells are required for the activation of gamma/delta T cells in the spleen. The second aim is to test the hypothesis that gamma/delta T cells, activated in ACAID, are antigen-specific, regulatory T cells. We will determine whether gamma/delta T cells induce CD8+, alpha/beta TCR to become efferent suppressor T cells in ACAID. Whether the gamma/delta T cells (and/or CD8+ suppressor effector T cells) express memory functions will be assessed using PLAP/Cre transgenic B6 mice. Finally, a new model using ROSA26R Tg mice will be used to test the hypothesis that ACAID inducing APC can be identified and tracked in vivo. Understanding the mechanisms of ACAID may one day be used to prevent graft rejection. Immune response by previously primed individuals can be inhibited by ACAID. Hence, understanding ACAID may also provide novel treatments for patients with autoimmune diseases after their symptoms arise.