Thymic Influence on Ocular Immunoregulation

胸腺对眼免疫调节的影响

• 批准号: 7070293
• 负责人: Robert E. Cone
• 金额: $ 37万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-05 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7070293
• 关键词: antigens; immunity; immunoregulation; spleen; thymus

DESCRIPTION (provided by applicant): The eye is protected from destructive innate and adaptive immune mechanisms by a local environment that is not conducive to immune-mediated reactions and by the ocular-induced regulation of systemic immunity. Active systemic regulation of destructive cell-mediated immunity is mediated by Anterior Chamber-Associated Immune Deviation (ACAID) imposed on the systemic immune system by complex cellular pathways in which circulating antigen presenting cells home to the thymus and to the spleen. In the thymus and spleen T lymphocytes that induce and effect the suppression of cell-mediated immunity are produced. Our laboratory has shown that after the intracameral injection of antigen (i) intracameral antigen but not intravenous antigen is found in the thymus;(ii) both iris monocytic cells and similar circulating monocytic cells activate immunoregulatory NK 1.1+ thymocytes that (i) enhance the production of lgG1 antibodies to the intracameral antigen and activate CD4+ and CD8+ splenic T cells that suppress cell-mediated immunity. To advance these studies we propose that the intracameral injection of antigen induces monocytic cells in the iris/ciliary body that activate thymic regulatory T cells and splenic immunoregulatory T cells that suppress systemic delayed-type hypersensitivity. To test this hypothesis we will (1) determine the mechanisms(s) by which intracameral antigen travels to the thymus and spleen, (2) determine the induction of regulatory thymocytes by monocytic cells derived from the iris. (3) Determine the mechanism(s) by which immunoregulatory thymocytes from donors receiving intracameral antigen activate splenic suppressor T cells. These studies are essential to a full definition of an oculo/thymic/splenic axis. This ocular-thymic link confirms an active role for the thymus and the eye in the regulation of systemic immunity that could impact on the management of inflammatory eye disease, corneal transplantation, ocular tumors and autoimmune disease.

描述（由申请人提供）：通过不利于免疫介导反应的局部环境以及眼睛诱导的全身免疫调节，保护眼睛免受破坏性先天和适应性免疫机制的影响。破坏性细胞介导的免疫的主动系统调节是由前房相关免疫偏差（ACAID）介导的，ACAID通过复杂的细胞途径强加于系统免疫系统，其中循环抗原呈递细胞归巢于胸腺和脾脏。在胸腺和脾脏中产生 T 淋巴细胞，其诱导并抑制细胞介导的免疫。我们的实验室表明，在前房注射抗原后，(i) 在胸腺中发现了前房内抗原，而不是静脉内抗原；(ii) 虹膜单核细胞和类似的循环单核细胞都激活了免疫调节性 NK 1.1+ 胸腺细胞，从而 (i) 增强了产生针对前房内抗原的 IgG1 抗体，并激活抑制细胞介导免疫的 CD4+ 和 CD8+ 脾 T 细胞。为了推进这些研究，我们提出前房注射抗原会诱导虹膜/睫状体中的单核细胞激活胸腺调节T细胞和脾脏免疫调节T细胞，从而抑制全身迟发型超敏反应。为了检验这一假设，我们将（1）确定前房内抗原传播至胸腺和脾脏的机制，（2）确定虹膜来源的单核细胞对调节性胸腺细胞的诱导。 (3) 确定接受前房内抗原的供体的免疫调节胸腺细胞激活脾抑制 T 细胞的机制。这些研究对于眼/胸腺/脾轴的完整定义至关重要。这种眼胸腺联系证实了胸腺和眼睛在调节全身免疫中的积极作用，这可能影响炎症性眼病、角膜移植、眼肿瘤和自身免疫性疾病的治疗。