CELLULAR PATHWAYS OF OCULAR IMMUNOREGULATION

眼部免疫调节的细胞途径

• 批准号: 6498365
• 负责人: Robert E. Cone
• 金额: $ 25.32万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6498365
• 关键词: CD antigens; T lymphocyte; anterior chamber; antigen presentation; biological signal transduction; cellular immunity; eye; immunologic assay /test; immunoregulation; interferon gamma; laboratory mouse; leukocyte activation /transformation; thymus; tissue /cell culture

DESCRIPTION (Adapted from applicant's abstract): The eye is often "protected" from damaging defense mechanisms brought forward for disturbances such as infection, inflammation and tumors. To accomplish this protection the ocular environment is usually non-permissive to inflammation and there is an ocular influence on systemic immune responses that ultimately could damage the eye. For example, the introduction of antigen into the anterior chamber results in the initiation of a T cell-mediated antigen-specific modulation of a systemic, cell-mediated immune response to the intracameral antigen. We have investigated relationships between the eye and the systemic immune response and have shown that (i) in adult mice an intact thymus is required for the suppression of cell-mediated immunity induced by the introduction of antigen into the anterior chamber (AC) and systemic immunization (ii) CD4-, CD8-, TCR alpha, beta+ thymocytes recovered from mice following an AC injection of antigen specifically transfer the suppression of cell-mediated immunity to naive or immunized mice, (iii) like immune suppression induced by AC injection and immunization, the suppression of cell-mediated immunity by thymocytes from AC-injected mice is effected by splenic T lymphocytes. (iv) Peripheral blood mononuclear cells from mice receiving intracameral antigen induce immunoregulatory thymocytes in recipient mice. Based on these observations we propose that the circulating cellular signal induced by intracameral antigen induces thymic immunoregulatory cells that migrate to the spleen. These recent thymic emigrants, activated by an ocular signal, induce and/or become immunoregulatory T cells that effect the regulation of cell-mediated immunity. To test this hypothesis, the Specific Aims of this application are to: (1) Define further the thymocyte-inducing "signal" produced after AC-injection of antigen. (2) Demonstrate that splenic immunoregulatory T cells induced by AC -injection of antigen are derived from and/or induced by immunoregulatory thymocytes. (3) Define the immunoregulatory mechanisms of immunoregulatory thymocytes and splenic T cells induced by AC injection of antigen. Ultimately, our studies could illuminate an oculoIthymic axis that introduces exogenous antigen to the thymus leading to the activation of immunoregulatory T cells. Understanding of this axis could impact on the management o f inflammatory eye disease, organ transplants (e.g. cornea), ocular tumors and autoimmune disease.

描述（改编自申请人的摘要）：眼睛经常受到“保护” 来自为干扰而提出的破坏性防御机制，例如 感染、炎症和肿瘤。为了实现这种保护眼睛 环境通常不允许炎症发生，并且存在眼部炎症 影响全身免疫反应，最终可能损害眼睛。 例如，将抗原引入前房会导致 T 细胞介导的全身性抗原特异性调节的启动， 针对前房内抗原的细胞介导的免疫反应。我们调查过 眼睛与全身免疫反应之间的关系已经表明 (i) 在成年小鼠中，需要完整的胸腺来抑制 通过将抗原引入前部诱导细胞介导的免疫 室 (AC) 和全身免疫 (ii) CD4-、CD8-、TCR α、β+ AC 注射抗原后从小鼠体内回收的胸腺细胞 特异性地将细胞介导的免疫抑制转移到幼稚或 免疫小鼠，(iii) 如 AC 注射诱导的免疫抑制和 免疫，抑制胸腺细胞介导的免疫 AC 注射小鼠受到脾 T 淋巴细胞的影响。 (四) 外周血 来自接受前房内抗原诱导的小鼠的单核细胞 受体小鼠的免疫调节胸腺细胞。根据这些观察，我们 提出由前房内抗原诱导的循环细胞信号 诱导胸腺免疫调节细胞迁移至脾脏。最近这些 胸腺移民，由视觉信号激活，诱导和/或成为 免疫调节 T 细胞影响细胞介导的免疫调节。 为了检验这一假设，本应用的具体目标是：(1) 进一步定义 AC 注射后产生的胸腺细胞诱导“信号” 抗原。 (2) 证明AC诱导脾脏免疫调节T细胞 - 抗原注射源自免疫调节和/或由免疫调节诱导 胸腺细胞。 (3)明确免疫调节的免疫调节机制 AC注射抗原诱导胸腺细胞和脾T细胞。最终， 我们的研究可以阐明引入外源性的眼胸腺轴 胸腺抗原导致免疫调节 T 细胞的激活。 了解该轴可能会影响眼部炎症的治疗 疾病、器官移植（例如角膜）、眼部肿瘤和自身免疫性疾病。