Caspi R R, Grubbs B G, Chan C C, Chader G J, Wiggert B
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1992 Apr 15;148(8):2384-9.
Experimental autoimmune uveoretinitis (EAU) in animals is a T cell-mediated autoimmune response directed against cells of the neural retina, in particular the photoreceptors. EAU can be induced in susceptible strains of mice by immunization with purified retinal Ag, and serves as a model for human uveitis. Because strong HLA associations have been noted in a number of human uveitic diseases, we investigated the role of MHC vs non-MHC genes in the control of susceptibility to ocular autoimmunity using the mouse EAU model. Selected strains representing most of the known independent H-2 haplotypes, as well as several H-2-recombinant and congenic strains, were immunized with interphotoreceptor retinoid-binding protein. Ocular pathology was induced in strains of the H-2k haplotype and their I-A-matched congenics, as well as in strains of the H-2r, H-2b, and H-2d haplotypes. In a series of experiments utilizing intra-H-2 recombinant strains, MHC control of susceptibility was tentatively mapped to the I-A subregion of the H-2k. Expression of the I-Ek gene product was not required for susceptibility to EAU, and in fact appeared to have an ameliorating effect on disease. Incidence and severity of disease obtained in strains sharing the same H-2 on a different background, or sharing the same background in the context of a different H-2, indicated that non-MHC genes contribute significantly to the regulation of EAU. Disease expression of susceptible H-2 haplotypes was highest in strains with B10 background (permissive) and ranged from intermediate to absent in strains with other (nonpermissive) backgrounds. The data suggest that although the ability to develop ocular pathology is dependent on the I-A subregion of the H-2, the final expression of disease in susceptible haplotypes is largely determined by background, non-MHC genes.
动物实验性自身免疫性葡萄膜视网膜炎（EAU）是一种针对神经视网膜细胞，尤其是光感受器的T细胞介导的自身免疫反应。通过用纯化的视网膜抗原免疫易感品系的小鼠可诱导出EAU，它可作为人类葡萄膜炎的模型。由于在许多人类葡萄膜炎疾病中已发现与HLA有很强的关联，我们使用小鼠EAU模型研究了MHC基因与非MHC基因在控制眼部自身免疫易感性中的作用。选用了代表大多数已知独立H-2单倍型的品系，以及几个H-2重组品系和同源近交系，用视网膜间视黄醇结合蛋白进行免疫。H-2k单倍型品系及其I-A匹配的同源近交系，以及H-2r、H-2b和H-2d单倍型品系均诱发了眼部病变。在一系列利用H-2内部重组品系的实验中，易感性的MHC控制初步定位于H-2k的I-A亚区。对EAU的易感性并不需要I-Ek基因产物的表达，实际上它似乎对疾病有改善作用。在不同背景下具有相同H-2的品系中，或在不同H-2背景下具有相同背景的品系中所获得的疾病发生率和严重程度表明，非MHC基因对EAU的调节有显著贡献。易感H-2单倍型的疾病表达在具有B10背景（允许性）的品系中最高，而在具有其他（非允许性）背景的品系中则从中等程度到无表达。数据表明，虽然发生眼部病变的能力取决于H-2的I-A亚区，但易感单倍型中疾病的最终表达很大程度上由背景非MHC基因决定。
