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Immunological and Clinical Analysis of Experimental Heat Shock Protein-Induced Uveitis

实验性热休克蛋白诱导葡萄膜炎的免疫学和临床分析

基本信息

批准号：
11671752
负责人：
UCHIO Eiichi
金额：
$ 2.11万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

We have already demonstrated that the heat shock protein (HSP) T cell peptide determinants which specifically stimulate T cells from patients with ocular type Behcet's disease (BD) are capable of both inducing uveitis and stimulating lymphocyte proliferation in rats. In the present study, mycobacterial HSF 65 kD and those peptides were injected into Lewis rats, and IgG and IgA antibodies (Abs) were measured using an enzyme-linked immunosorbent assay (ELISA). Serum collected 21 days after immunization of HSP peptides from rats that developed uveitis showed significantly higher IgG Ab levels to peptide 311-326 and 336-351 than did serum samples collected from rats without uveitis. Significant elevation of levels of IgA Abs in rats that developed uveitis was also observed in rats immunized with 111-125, 311-326 and 336-351. 1. In rats injected with HSP 65 kD, the IgG Ab levels to peptide 111-125, 154-172 and 311-326 showed a considerable increase and the IgA Ab level to peptide 311-326 also showed a marked elevation. Marked inhibition of IgG Ab binding to HSP 65 kD by peptides 111-125, 154-172, 311-326 and 336-351 and of IgA Ab binding by peptides 311-326 and 336-351 were observed in rats immunized with HSP 65 kD. These results suggest that the epitopes responsible for ocular disease development and antibody production in rats injected with HSP 65 kD might be similar or identical to those that are most immunogenic for T cells from patients with ocular type BD, and that IgA Abs play a similar or more critical and important role compared with IgG Abs in the development and progression of HSP-induced uveitis, and that they can be used as markers of disease activity.

我们已经证明，热休克蛋白（HSP）的T细胞肽决定簇，特异性刺激T细胞从患者眼型白塞病（BD）能够诱导葡萄膜炎和刺激淋巴细胞增殖的大鼠。在本研究中，分枝杆菌HSF 65 kD和这些肽注射到刘易斯大鼠，并使用酶联免疫吸附测定（ELISA）测定IgG和伊加抗体（Abs）。HSP肽免疫后21天从发生葡萄膜炎的大鼠收集的血清显示出比从没有葡萄膜炎的大鼠收集的血清样品显著更高的针对肽311-326和336-351的IgG Ab水平。在用111-125、311-326和336-351免疫的大鼠中也观察到发生葡萄膜炎的大鼠中伊加Ab水平显著升高。1.注射HSP 65 kD的大鼠，对111-125、154-172和311-326肽的IgG抗体水平明显升高，对311-326肽的伊加抗体水平也明显升高。在HSP 65 kD免疫的大鼠中观察到肽111-125、154-172、311-326和336- 351显著抑制IgG Ab与HSP 65 kD的结合，肽311-326和336 -351显著抑制伊加Ab与HSP 65 kD的结合。这些结果表明，在注射HSP 65 kD的大鼠中负责眼部疾病发展和抗体产生的表位可能与来自眼部型BD患者的T细胞的最具免疫原性的表位相似或相同，并且与IgG Ab相比，伊加Ab在HSP诱导的葡萄膜炎的发展和进展中起相似或更关键和重要的作用，并且它们可以被用作疾病活动的标记。