Neuroimmunomodulation within the eye

描述(由申请人提供)：眼睛通常具有唯一的 局部改变免疫表达的生理适应。 这种生理适应是眼睛免疫特免权的一部分。这个 免疫特免权的生理作用是赋予眼睛免疫力 避免免疫原性的破坏性副作用的保护 发炎。与迟发型超敏反应相关的免疫原性炎症 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到选择性缺陷。 迟发性超敏T细胞。为了控制免疫原性炎症， 眼部微环境中的细胞和神经元产生 局部抑制T细胞炎症介质的免疫调节因子 活动。对房水的生化检查表明，一些 其免疫抑制活性与刺激α-黑素细胞有关 激素(α-MSH)。通过α-MSH，房水抑制干扰素-γ 但促进产生转化生长因子-β的效应性T细胞的增殖。 这些效应T细胞作为调节性T细胞发挥作用，因为它们可以抑制 其他炎性T细胞介导的免疫性炎症。此外，如果 这种调节性T细胞对眼睛自身抗原有特异性反应，它们可以 抑制自身免疫性视网膜炎的严重程度和发病率。的归纳 调节性T细胞是α-MSH影响抗原能力的结果 递呈细胞(APC)激活T细胞并直接作用于T细胞 呈递给抗原。我们的计划是描述阿尔法-MSH的影响 T细胞活化机制的研究。我们还将测试以下可能性 注射α-MSH本身或α-MSH诱导的调节性T细胞 可以抑制眼部自身免疫性疾病的发病率和严重程度。这个 这个项目的结果将使我们能够理解分子和细胞 正常眼睛的免疫力特征。通过了解人类的活动 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清除 没有免疫原性炎症的致盲后果，这会阻止或 治愈眼睛的自身免疫性疾病，促进角膜手术的成功， 视网膜和其他组织移植。

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.