权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study of experimental autoimmune uveoretinitis

实验性自身免疫性葡萄膜视网膜炎的研究

基本信息

批准号：
03670187
负责人：
TAGUCHI Osamu
金额：
$ 1.28万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670187/
关键词：
uveoretinitis nude mouse autoimmune disease thymic chimera IRBP thymus ヌ-ドマウス

项目摘要

This paper describes the spontaneous occurrence of an autoimmune uveoretinitis in nude (nu/nu) mice reconstituted when 4 weeks old by the grafting of rat embryonic thymus (TG nude). The uveoretinitis was characterized histologically by progressive loss of the photoreceptor layer, observed in 4.0, 17.6, 42.9 and 71.4 percent of such mice at 3, 5, 7 and 12 months of age, respectively. Mice with uveoretinitis were shown to have serum IgG antibody reactive by indirect immunofluorescence with retinal photoreceptors, and with interphotoreceptor retinoid-binding protein (IRBP), but not retinal S-antigen, by immunoblotting and ELISA. IRBP is an approximately 140 kDa glycoprotein consisting of about 1260 amino acid residues. We found that residues 1182-1194 is the immunodominant determinant in TG nude mice, and that tryptophan at residue 1182 and proline at residue 1194 are agretopes of the peptide. A uveoretinitis could be adoptively transferred to syngeneic ungrafted nude mice by splenic CD4-positive T cells from diseased animals. This is the first experimental model of a (T-cell mediated) autoimmune uveoretinitis which develops spontaneously and which is not dependent upon deliberate sensitization with retinal antigens and adjuvants.

本文描述了在 4 周大时通过移植大鼠胚胎胸腺（TG 裸鼠）重建的裸鼠（nu/nu）中自发发生的自身免疫性葡萄膜视网膜炎。葡萄膜视网膜炎的组织学特征是感光层进行性丧失，在 3、5、7 和 12 个月龄的此类小鼠中分别观察到 4.0%、17.6%、42.9% 和 71.4% 的小鼠。通过间接免疫荧光法显示，患有葡萄膜视网膜炎的小鼠血清 IgG 抗体与视网膜光感受器和光感受器间视黄酸结合蛋白 (IRBP) 发生反应，但通过免疫印迹和 ELISA 不与视网膜 S 抗原发生反应。 IRBP 是一种约 140 kDa 的糖蛋白，由约 1260 个氨基酸残基组成。我们发现残基1182-1194是TG裸鼠的免疫显性决定簇，并且残基1182处的色氨酸和残基1194处的脯氨酸是肽的聚集位。葡萄膜视网膜炎可通过患病动物的脾脏 CD4 阳性 T 细胞过继转移至同基因未移植裸鼠。这是（T 细胞介导的）自身免疫性葡萄膜视网膜炎的第一个实验模型，该模型自发发生且不依赖于视网膜抗原和佐剂的故意致敏。