Regulation of Ocular Tolerance by Gamma/delta T Cells

γ/δ T 细胞对眼耐受性的调节

• 批准号: 6318736
• 负责人: JUDITH A KAPP
• 金额: $ 30.45万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6318736
• 关键词: RNase protection assay; T cell receptor; T lymphocyte; anterior chamber; antigen presenting cell; cell cell interaction; cell migration; cytotoxic T lymphocyte; eye; gene targeting; genetically modified animals; helper T lymphocyte; immune tolerance /unresponsiveness; immunologic memory; immunoregulation; laboratory mouse; molecular cloning; natural killer cells; suppressor T lymphocyte; transfection

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.

描述（由申请人提供）：眼睛是一种免疫特权 移植组织比传统部位存活更长时间的部位， 例如皮肤。此外，细胞和可溶性抗原都被放置在 眼睛的前房诱导全身形式的耐受，称为ACAID， 其中迟发性超敏反应和补体固定抗体对 抗原的免疫原性形式被抑制。我们最近的研究 表明细胞溶解性T细胞应答的诱导也是深刻的， 在接受眼抗原的小鼠中抑制。我们的数据还显示， 在γ/δ T细胞耗尽的小鼠中不诱导耐受性， 正常小鼠脾γ/δ T细胞过继转移 重建宽容。 拟议研究的长期目标是通过以下方式确定机制： 其中γ/δ T细胞调节眼耐受性，如CD 4和CD 8中所示 T细胞反应。我们将检验ACAID诱导 抗原呈递细胞和NK α/β T细胞是免疫系统的必需。 脾中γ/δ T细胞的活化。第二个目标是测试 假设在ACAID中活化的γ/δ T细胞是抗原特异性的， 调节性T细胞我们将确定γ/δ T细胞是否诱导CD 8+， 在ACAID中，α/β TCR成为传出抑制性T细胞。是否 γ/δ T细胞（和/或CD 8+抑制效应T细胞）表达记忆 将使用PLAP/Cre转基因B6小鼠评估功能。最后，新的 使用ROSA 26 R Tg小鼠的模型将用于检验ACAID 可以在体内识别和追踪诱导APC的细胞。 了解ACAID的机制可能有一天可以用来防止移植 排斥反应先前致敏个体的免疫应答可被以下物质抑制： 很好。因此，了解ACAID也可能为治疗提供新的治疗方法。 自身免疫性疾病患者出现症状后。