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）：眼睛通常是“受保护的” 从破坏防御机制引起的骚乱，例如 感染，炎症和肿瘤。为了实现此保护 环境通常不适合炎症，并且有眼 对最终可能损害眼睛的系统性免疫反应的影响。 例如，将抗原引入前腔导致 T细胞介导的全身性调制的启动 细胞介导的对腔内抗原的免疫反应。我们已经调查了 眼睛与全身免疫反应之间的关系，已显示 （i）在成年小鼠中 细胞介导的免疫力通过将抗原引入前面引起 腔室（AC）和全身免疫（II）CD4-，CD8-，TCR Alpha，beta+ 注射抗原后，从小鼠中回收的胸腺细胞 特异性地将细胞介导的免疫抑制至幼稚或 免疫的小鼠，（iii）如AC注射引起的免疫抑制和 免疫，胸腺细胞抑制细胞介导的免疫力 注射AC的小鼠受脾脏T淋巴细胞的影响。 （iv）外周血 接受腔内抗原的小鼠的单核细胞诱导 受体小鼠的免疫调节性胸腺细胞。根据这些观察，我们 提出由腔内抗原诱导的循环细胞信号 诱导胸膜免疫调节细胞，这些细胞迁移到脾脏。这些最近 胸腺移民，被眼信号激活，诱导和/或变为 影响细胞介导的免疫力调节的免疫调节T细胞。 为了检验这一假设，该应用的具体目的是：（1） 进一步定义在注射AC注入后产生的胸腺细胞诱导的“信号” 抗原。 （2）证明AC诱导的脾脏免疫调节T细胞 - 抗原的注射是由免疫调节的和/或诱导的 胸腺细胞。 （3）定义免疫调节的免疫调节机制 通过AC注射抗原诱导的胸腺细胞和脾脏T细胞。最终， 我们的研究可以照亮引入外源性的动力轴 与胸腺的抗原导致免疫调节T细胞的激活。 了解该轴可能会影响炎症眼的管理 疾病，器官移植（例如角膜），眼部肿瘤和自身免疫性疾病。