IMMUNOHISTOCHEMICAL ANALYSIS OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU) INDUCED BY INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP) IN THE RAT
IMMUNOHISTOCHEMICAL ANALYSIS OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU) INDUCED BY INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP) IN THE RAT
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DOI：
10.3109/08820138709055713
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发表时间：
1987-01-01
影响因子：
2.8
通讯作者：
GERY, I
中科院分区：
文献类型：
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作者：
CHAN, CC;NUSSENBLATT, RB;GERY, I
用牛视网膜光感受器间维甲酸结合蛋白（IRBP）诱导大鼠实验性自身免疫性葡萄膜视网膜炎（EAU），并进行免疫组化研究。一般而言，IRBP诱导炎症细胞成分和免疫相关抗原在各种非淋巴细胞上的表达与S抗原（S-Ag）引起的相似。但两种疾病之间存在差异，包括：1）IRBP EAU中T抑制细胞/细胞毒性细胞的增加比S-Ag EAU更快。2)IRBP EAU中表达主要组织相容性复合物II类表面抗原的非淋巴细胞数量少于S-Ag EAU。本文对这两种视网膜抗原诱发EAU的免疫发病机制进行了讨论。S-抗原（S-Ag），分子量为78 K，约占视网膜和松果体总可溶性蛋白的0.5%和0.2%。它含有非常少量的磷脂和一些碳水化合物部分。它主要位于视杆外节的细胞膜上，并已被定义为通过结合到感光细胞的外节膜对光信号作出反应。实验性自身免疫性葡萄膜视网膜炎（EAU）是通过免疫在动物中诱导的T细胞依赖性免疫反应，最常见的是使用视网膜特异性蛋白S-抗原（S-Ag）（1-3）。我们通过免疫组织化学技术研究了该动物模型中炎症眼组织中淋巴细胞亚群的动态变化（4）。在急性炎症反应后疾病的早期阶段，T辅助/诱导淋巴细胞在浸润细胞中的数量较多，T抑制/细胞毒性淋巴细胞的相对数量非常低。在后期阶段，浸润内T抑制细胞/细胞毒性细胞的相对数量持续增加。用同样的方法，我们还报道了S-Ag诱导的EAU大鼠视网膜色素上皮（RPE）和视网膜血管内皮细胞表达主要组织相容性复合物（MHC）Ⅱ类（Ia和IE）抗原。最近，牛感光细胞间类维生素A结合蛋白（IRBP），一种存在于视网膜感光细胞间基质中的细胞外糖蛋白（表观Mr为133 K Da），已被分离和表征（7）。与S-Ag一样，它位于视网膜和松果体中;与S-Ag不同，少量IRBP存在于大脑皮层中。其生物学功能被认为与类维生素A在视网膜和视网膜色素上皮之间的转运有关。IRBP被发现是一种有效的致葡萄膜炎分子，产生的EAU在临床和组织病理学上都与S-Ag诱导的EAU相似（8，9）。这两种实验性疾病的不同之处在于：（a）IRBP诱导的EAU的病程较短;和（B）尽管IRBP在低剂量（< 5 μ g/大鼠）下更易致葡萄膜炎，但S-Ag在较高剂量（> 20 μ g/大鼠）下诱导更严重的变化（8）。此外，我们未发表的数据表明，这两种抗原在不同近交系大鼠中的葡萄膜致敏性明显不同。本研究的目的是（a）鉴定在不同阶段浸润眼睛的淋巴细胞和（B）检查在IRBP诱导的EAU期间各种非淋巴细胞上Ia和Ie抗原的表达。
Experimental autoimmune uveoretinitis (EAU) was induced in rats by immunization with bovine interphotoreceptor retinoid-binding protein (IRBP) and studied by immunohistochemistry. In general, the IRBP induction of inflammatory cellular components and expression of immune-related antigens on various non-lymphoid cells resembled those provoked by S-antigen (S-Ag). However, differences were found between the two diseases, including: 1) The increase in T suppressor/cytotoxic cells occurred in IRBP EAU more rapidly than in S-Ag EAU. 2) Fewer numbers of non-lymphoid cells expressed major histocompatibility complex class II surface antigens in IRBP EAU than in S-Ag EAU. The immunopathogenic mechanisms of EAU induced by these two retinal antigens are discussed. S-antigen (S-Ag), with molecular weight of 78K, comprises approximately 0.5% and 0.2% of the total soluble protein of the retina and the pineal gland. It contains a very small amount of phospholipid and a few carbohydrate moieties. It is located mainly on the cellular membrane of the rod outer segment and has been defined to react to light signals by binding to the outer segment membrane of the photoreceptor cells. Experimental autoimmune uveoretinitis (EAU) is a T cell dependent immune reaction induced in animals by immunization, most commonly with the retinal-specific protein, S-antigen (S-Ag) (1-3). We studied the dynamic changes of the lymphocyte subsets in the inflamed ocular tissue in this animal model by immunohistochemical techniques (4). During the early stages of the disease following the acute inflammatory reaction, the T helper/inducer lymphocytes are found in larger numbers within the infiltrates and the relative number of the T suppressor/cytotoxic lymphocytes is very low. During the later stages, there is a continuous increase in the relative number of T suppressor/cytotoxic cells within the infiltrates. Using the same method, we also reported that the retinal pigment epithelium (RPE) and the retinal vascular endothelium could express major histocompatibility complex (MHC) class II (Ia and IE) antigens in the rats developing S-Ag induced EAU. Recently, bovine interphotoreceptor retinoid-binding protein (IRBP), an extracellular glycoprotein (apparent Mr of 133 K Da), present in the retinal interphotoreceptor matrix, has been isolated and characterized (7). Like S-Ag, it locates in the retina and pineal gland; unlike S-Ag, small amounts of IRBP are present in the brain cortex. Its biological functions are thought to be related to transport of retinoids between the retina and the retinal pigment epithelium. IRBP was found to be a potent uveitogenic molecule, and produced an EAU which resembled that induced by S-Ag both clinically and histopathologically (8,9). The two experimental diseases differ in that: (a) the course of disease is shorter in EAU induced by IRBP; and (b) although IRBP is more uveitogenic at low doses (< 5 .mu.g/rat), S-Ag induces more severe changes at higher doses (> 20 .mu.g/rat) (8). In addition, our unpublished data show that these two antigens differ markedly in their uveitogenicity among rats of various inbred strains. The present study was aimed at (a) identifying the lymphocytes which infiltrate the eye at various stages and (b) examining the expression of Ia and Ie antigens on various non-lymphoid cells during IRBP- induced EAU.