Analysis of T cell Tolerance induction against the retinal self- antigen IRBP

T 细胞对视网膜自身抗原 IRBP 的耐受诱导分析

基本信息

批准号：
05671476
负责人：
USUI Masahiko
金额：
$ 1.15万
依托单位：
Tokyo Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671476/
关键词：
IRBP Uveoretinitis tolerance ぶどう膜網膜炎自己免疫病

项目摘要

Interphotoreceptor retinoid-binding protein (IRBP), which localizes specifically in the retina and the pineal gland, has been found to be highly immunopathogenic and capable of inducing experimental autoimmune uveoretinitis in a variety of animal species. However, since self-antigens such as IRBP normally exist in the body without causing uveoretinitis, it follows that self tolerance usually develops is still poorly understood. Nevertheless, recent work has provided direct evidence that T cell tolerance can occur by at least two different mechanisms involving interaction with self-antigens : clonal deletion in the thymus, and anergy in the periphery. In this study, we investigated whether endogenous IRBP also influences the induction of T cell tolerance against it. To that end, we removed the eyes and pineal glands of nude mice to eliminate endogenous IRBP,and reconstituted their T cell function by embryonic syngenic mouse thymus grafting (OxPxTg nude mice). Then, when we examined the lymphocyte response of the OxPxTg mice stimulated with IRBP,the significant proliferative response and production of IL-2 were observed, but not to be shown in that of normal BALB/c mice. Moreover, an IRBP specific T cell line established from the OxPxTg nude mice transferred into intact BALB/c nude mice was capable of inducing uveoretinitis. As a result of these findings, we elucidated that the organ-specific self-antigen IRBP is not merely the target antigen of the autoimmune disease known as uveoretinitis, but in the normal state it is also involved in the acquisition of T cell tolerance to itself (IRBP).

光感受器间视黄醇结合蛋白（IRBP）专门位于视网膜和松果体中，已被发现具有高度免疫致病性，并且能够在多种动物物种中诱发实验性自身免疫性葡萄膜视网膜炎。然而，由于IRBP等自身抗原通常存在于体内而不会引起葡萄膜视网膜炎，因此对于自身耐受性通常如何发展仍知之甚少。然而，最近的工作提供了直接证据，表明 T 细胞耐受性可以通过至少两种涉及与自身抗原相互作用的不同机制发生：胸腺中的克隆缺失和外周的无反应性。在这项研究中，我们研究了内源性 IRBP 是否也会影响 T 细胞对其耐受的诱导。为此，我们摘除裸鼠的眼睛和松果体以消除内源性IRBP，并通过胚胎同基因小鼠胸腺移植（OxPxTg裸鼠）重建其T细胞功能。然后，当我们检查IRBP刺激的OxPxTg小鼠的淋巴细胞反应时，观察到显着的增殖反应和IL-2的产生，但在正常BALB/c小鼠中未观察到。此外，从OxPxTg裸鼠建立的IRBP特异性T细胞系转移到完整的BALB/c裸鼠中能够诱导葡萄膜视网膜炎。根据这些发现，我们阐明器官特异性自身抗原 IRBP 不仅是称为葡萄膜视网膜炎的自身免疫性疾病的靶抗原，而且在正常状态下，它还参与 T 细胞对其自身耐受的获得（IRBP）。