Singh V K, Usukura J, Shinohara T
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD 20892.
Jpn J Ophthalmol. 1992;36(1):108-16.
S-antigen (S-Ag), a well characterized 45-kDa protein in the photoreceptor cells, induces predominantly T-cell-mediated autoimmune uveitis when injected into experimental animals. Recently, we have shown that native histone H3 protein derived from yeast (Saccharomyces cerevisiae), or a synthetic peptide that is homologous with S-Ag peptide M in having six consecutive amino acids, induces experimental autoimmune uveitis (EAU) similar to that induced by native S-Ag in the Lewis rat. In this study, monkeys (Macaca fascicularis) immunized with histone H3 peptide developed a strong cellular immune response to this peptide as well as to peptide M. However, no significant inflammation or hypervascularization was observed in the retina or the iris during the experimental period, when they were examined clinically with an inverted ophthalmoscope. Histopathological examination showed that all monkeys injected with histone H3 peptide or with native histone H3 lost a large number of photoreceptor rod cells and developed neovascularization in the outer nuclear cell layer of the retina. These histopathological findings in the monkey retina closely resemble those seen in human patients with some types of uveitis. The possible involvement of microbial proteins having sequence homology with normal retinal proteins in the pathogenicity of human uveitis is discussed.
S抗原（S-Ag）是一种在光感受器细胞中特性明确的45千道尔顿蛋白质，当注入实验动物体内时，主要诱导T细胞介导的自身免疫性葡萄膜炎。最近，我们发现源自酵母（酿酒酵母）的天然组蛋白H3蛋白，或与S-Ag肽M具有六个连续氨基酸同源性的合成肽，在Lewis大鼠中诱导出与天然S-Ag相似的实验性自身免疫性葡萄膜炎（EAU）。在本研究中，用组蛋白H3肽免疫的猴子（食蟹猴）对该肽以及肽M产生了强烈的细胞免疫反应。然而，在实验期间，当用间接检眼镜进行临床检查时，在视网膜或虹膜中未观察到明显的炎症或血管增生。组织病理学检查显示，所有注射组蛋白H3肽或天然组蛋白H3的猴子都失去了大量的视杆细胞，并在视网膜外核细胞层出现了新生血管形成。猴子视网膜中的这些组织病理学发现与某些类型葡萄膜炎的人类患者所见非常相似。本文讨论了与正常视网膜蛋白具有序列同源性的微生物蛋白在人类葡萄膜炎发病机制中的可能作用。
