Neuroimmunomodulation within the eye

眼内的神经免疫调节

• 批准号: 6819721
• 负责人: Andrew W Taylor
• 金额: $ 32.55万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6819721
• 关键词: RNase protection assay; T lymphocyte; anterior chamber; autoimmune disorder; denervation; enzyme linked immunosorbent assay; flow cytometry; genetically modified animals; inflammation; interferon gamma; interleukin 4; laboratory mouse; leukocyte activation /transformation; melanocyte stimulating hormone; neuroimmunomodulation; polymerase chain reaction; transforming growth factors; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): The eye normally possesses a unique physiological adaptation that regionally modifies the expression of immunity. This physiological adaptation is part of ocular immune privilege. The physiological role of immune privilege is to impart upon the eye immune protection that avoids the destructive side effects of immunogenic inflammation. Immunogenic inflammation associated with delayed hypersensitivity reactions can grossly distort the visual axis resulting in blindness. Consequently, immune protection within the eye involves a selective deficiency of delayed type hypersensitivity T-cells. To control immunogenic inflammation, the cells and neurons within the ocular microenvironment produce immunomodulating factors that regionally suppress T-cell inflammatory-mediating activities. A biochemical examination of aqueous humor has shown that some of its immunosuppressive activity is associated with alpha-melanocyte stimulating hormone (alpha-MSH). Through alpha-MSH, aqueous humor suppresses IFN-gamma production but promotes proliferation of TGF-beta-producing effector T cells. These effector T cells act as regulatory T cells in that they can suppress immunogenic inflammation mediated by other inflammatory T cells. Moreover, if such regulatory T cells respond specifically to ocular autoantigens, they can suppress the severity and incidence of autoimmune retinitis. The induction of regulatory T cells is a result of alpha-MSH influencing the ability of antigen presenting cells (APC) to activate T cells and directly on T cells responding to presented antigen. It is our plan to characterize the effects of alpha-MSH on the mechanisms of T cell activation. We will also test the possibility that an injection of either alpha-MSH itself or alpha-MSH-induced regulatory T cells can suppress the incidence and severity of ocular autoimmune disease. The results of this project will allow us to understand the molecular and cellular features of immunity within the normal eye. By understanding the activity of intraocular immunomodulatory factors, such as alpha-MSH, it will be possible to induce an immune response that promotes the elimination of pathogens and tumors without the blinding consequences of immunogenic inflammation, that prevents or cures autoimmune diseases of the eye, and that promotes success of corneal, retinal and other tissue transplants.

描述（由申请人提供）：眼睛通常具有独特的 局部改变免疫表达的生理适应。 这种生理适应是眼部免疫豁免的一部分。的 免疫赦免的生理作用是赋予眼睛免疫 保护，避免了免疫原性的破坏性副作用， 炎症与迟发性超敏反应相关的免疫原性炎症 这些反应会严重扭曲视轴，导致失明。 因此，眼睛内的免疫保护涉及选择性缺陷， 迟发型超敏反应T细胞为了控制免疫原性炎症， 眼睛微环境中的细胞和神经元产生 局部抑制T细胞炎症介导的免疫调节因子 活动对眼房水的生化检查表明， 其免疫抑制活性与α-黑素细胞刺激有关 激素（α-MSH）。通过α-MSH，房水抑制IFN-γ 产生TGF-β，但促进产生TGF-β的效应T细胞增殖。 这些效应T细胞作为调节T细胞，因为它们可以抑制 免疫原性炎症由其他炎性T细胞介导。而且如果 这种调节性T细胞对眼自身抗原有特异性应答，它们可以 抑制自身免疫性视网膜炎的严重程度和发病率。的诱导 调节性T细胞是α-MSH影响抗原能力的结果 提呈细胞（APC）激活T细胞并直接作用于T细胞应答 呈递的抗原。我们的计划是描述α-MSH的作用 T细胞激活机制的研究我们还将测试 注射α-MSH本身或α-MSH诱导的调节性T细胞 可抑制眼部自身免疫性疾病的发病率和严重程度。的 该项目的结果将使我们能够了解分子和细胞 正常眼内的免疫功能。通过了解 眼内免疫调节因子，如α-MSH，将有可能 诱导免疫反应，促进病原体和肿瘤的消除 没有免疫原性炎症的致盲后果， 治愈眼睛的自身免疫性疾病，并促进角膜的成功， 视网膜和其他组织移植。