Residues 1-20 of IRBP and whole IRBP elicit different uveitogenic and immunological responses in interferon gamma deficient mice
Residues 1-20 of IRBP and whole IRBP elicit different uveitogenic and immunological responses in interferon gamma deficient mice
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DOI：
10.1006/exer.2000.0860
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发表时间：
2000-08-01
影响因子：
3.4
通讯作者：
Caspi, RR
中科院分区：
文献类型：
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作者：
Avichezer, D;Chan, CC;Caspi, RR
实验性自身免疫性葡萄膜视网膜炎(EAU)是一种T细胞介导的自身免疫性疾病，通过免疫葡萄膜原性视网膜抗原或过继转移Th-L样表型的葡萄膜原性T细胞而引起。我们先前已经证明，C57BL/6背景上的干扰素-γ缺陷小鼠(GKO)与野生型(WT)一样对光感受器间视黄酸结合蛋白(IRBP)诱导的EAU敏感。在本研究中，我们评估了新描述的人IRBP残基1-20中包含的11-2(B)表位对GKO小鼠EAU的诱导作用，并与整个IRBP分子的反应进行了比较。与以前的IRBP诱导的EAU相似，GKO小鼠的迟发型超敏反应(DTH)和淋巴细胞增殖反应以及IL-5和TNF-α的产生也增加。然而，与整个IRBP诱导的反应不同的是，该多肽没有产生令人愉快的IL-IO。免疫后第21天组织病理学检查。结果显示，GKO和WT小鼠均出现视网膜损害，包括感光细胞层受损、血管炎和炎性细胞浸润，但GKO小鼠的疾病评分明显高于GKO小鼠，且仅在GKO小鼠中观察到视网膜脱离。与野生型相比，GKO小鼠眼部的细胞浸润物中含有显著的嗜酸性粒细胞成分，尽管在多肽诱导的EAU中所占比例低于IRBP诱导的EAU。我们的结论是，对人肽1-20的细胞因子和炎症反应明显不同于对全牛IRBP的反应，这可能是GKO小鼠EAU评分高于野生型的原因。
Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated autoimmune disease induced by immunization with uveitogenic retinal antigens, or by the adoptive transfer of uveitogenic T-cells of the Th-l-like phenotype. We have previously shown that IFN-gamma-deficient mice (GKO) on the C57BL/6 background are equally susceptible to interphotoreceptor retinoid binding protein (IRBP)-induced EAU as the wild type (WT). In the present study, we evaluated EAU induction in GKO mice by the newly described 11-2(b) epitope contained in residues 1-20 of human IRBP, and compared it to the response to the whole IRBP molecule. Similarly to previous observations with IRBP-induced EAU, delayed type hypersensitivity (DTH) and lymphocyte proliferation responses were elevated in GKO mice, as was production of IL-5 and TNF-alpha. However unlike the responses induced by whole IRBP, there was no delectable IL-IO production to the peptide. Histopathology on day 21 after immunization. revealed that both GKO and WT mice developed retinal lesions, including damage to the photoreceptor cell layer, vasculitis and inflammatory cellular infiltration, but disease scores were significantly higher in GKO, and retinal detachment was observed only in GKO mice. In contrast to the wild type, the cellular infiltrate in eyes of GKO mice contained a prominent component of eosinophils, although of lower proportion in peptide-induced than in IRBP-induced EAU. We conclude that the cytokine and inflammatory responses to human peptide 1-20 differ perceptibly from the responses to whole bovine IRBP, and may explain the elevated EAU scores of GKO mice compared to wild type.