IMMUNE RESPONSES TO OCULAR ANTIGENS

对眼抗原的免疫反应

• 批准号: 6432438
• 负责人: Igal Gery
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432438
• 关键词: B lymphocyte; T cell receptor; antigen presentation; autoantigens; autoimmune disorder; cellular immunity; crystallins; disease /disorder model; eye disorder; eye infections; gene targeting; genetically modified animals; immune tolerance /unresponsiveness; immunosuppression; inflammation; laboratory mouse; lens proteins; leukocyte activation /transformation; lysozyme

Targeted at learning about inflammatory eye diseases, this project focused in FY 2000 on pathogenic mechanisms of immune-mediated ocular inflammation and cellular processes that regulate immunity against ocular antigens. Noteworthy results include the following: 1.A new experimental system was developed in order to learn about the involvement of different subsets of CD4 T-helper (Th) cells in ocular inflammation. This system determines the capacity of purified populations of Th1 and Th2 cells sensitized against hen egg lysozyme (HEL) to induce inflammation in eyes of mice in which HEL is transgenically expressed in the lens. Purified Th1 lymphocytes were highly pathogenic, producing ocular inflammation at numbers as low as 120,000. In contrast, Th2 cells failed to produce disease even at 30 million per recipient. Th2 cells did induce inflammation, however, when injected into recipients that were irradiated with a sub-lethal dose of 450 Rad. Adding Th2 cells had no effect on disease induced by Th1 in unirradiated mice, but enhanced the inflammation in irradiated recipients. These data indicate that the notion about Th2 cells being "protective" against immune-mediated inflammation is not necessarily correct. 2.The process of tolerance against self ocular antigens was further examined by using Tg mice that express HEL under the control of the alphaA-crystallin promoter ("HEL-Tg" mice). These mice are tolerant by their T-cell compartment against HEL. In addition, HEL-Tg mice fail to develop humoral immune response when immunized with HEL, but our new data show that the B-cell compartment is not tolerized against HEL and can produce antibody when provided with T-cell help. Thus, adoptive transfer of as few as 40,000 HEL-specific Th cells enabled production of substantial levels of HEL antibody in the HEL-Tg mice. Our results provide an experimental model for the process that facilitates production of pathogenic anti crystallin antibody in patients with lens-associated uveitis ("phacoanaphylactic endophthalmitis").

该项目针对学习炎症性眼部疾病，以2000财年为重点介绍了免疫介导的眼部炎症的致病机制和调节对眼抗原免疫力的细胞过程。值得注意的结果包括以下内容：1。开发了一个新的实验系统，以了解CD4 T-Helper（Th）细胞在眼部炎症中的不同子集的参与。该系统确定了对鸡蛋溶菌酶（HEL）敏感的Th1和Th2细胞纯化群体的能力，以诱导在透镜中转基因表达HEL的小鼠眼睛的炎症。纯化的Th1淋巴细胞具有高度致病性，可在低至120,000的数字下产生眼部炎症。 相比之下，TH2细胞即使以每位受体3000万的疾病产生疾病。 然而，当将炎症注射到受辐照的受体剂量450 rad的受体中时，Th2细胞确实会诱发炎症。添加Th2细胞对未辐照小鼠Th1诱导的疾病没有影响，但增强了受辐射受体的炎症。这些数据表明，关于Th2细胞对免疫介导的炎症的概念不一定是正确的。 2.通过使用在α-crystallin启动子（“ Hel-TG”小鼠）控制下表达HEL的TG小鼠，进一步检查了对自眼抗原的耐受性。 这些小鼠的T细胞隔室对HEL具有耐受性。此外，HEL-TG小鼠在用HEL免疫时无法产生体液免疫反应，但是我们的新数据表明，B细胞室对HEL不耐受，并且在提供T细胞帮助时可以产生抗体。 因此，少于40,000个HEL特异性的TH细胞的继产传递能够产生HEL-TG小鼠中大量的HEL抗体。我们的结果提供了一个实验模型，用于促进与晶状体相关葡萄膜炎患者（“ phacoanaganyphylactic conceric consectic toperpophatic thalmitis”）的致病性抗晶体抗体产生的过程。