Study of experimental autoimmune uveoretinitis

本文报道了用大鼠胚胎胸腺（TG nude）移植4周龄的裸小鼠（nu/nu）自发发生的自身免疫性葡萄膜视网膜炎。葡萄膜视网膜炎的组织学特征是感光层的进行性丧失，在3、5、7和12月龄的这些小鼠中分别观察到4.0%、17.6%、42.9%和71.4%。通过间接免疫荧光法，葡萄膜视网膜炎小鼠的血清IgG抗体可与视网膜光感受器反应，通过免疫印迹法和ELISA法，可与光感受器间类维生素A结合蛋白（IRBP）反应，但不与视网膜S抗原反应。IRBP是由约1260个氨基酸残基组成的约140 kDa的糖蛋白。结果表明，1182-1194位残基是TG裸鼠的免疫显性决定簇，1182位残基的色氨酸和1194位残基的脯氨酸是该肽的一致表位。葡萄膜视网膜炎可以通过来自患病动物的脾CD 4阳性T细胞过继转移到同系未移植裸小鼠。这是第一个实验模型的（T细胞介导的）自身免疫性葡萄膜视网膜炎，其自发发展，这是不依赖于故意致敏与视网膜抗原和佐剂。

This paper describes the spontaneous occurrence of an autoimmune uveoretinitis in nude (nu/nu) mice reconstituted when 4 weeks old by the grafting of rat embryonic thymus (TG nude). The uveoretinitis was characterized histologically by progressive loss of the photoreceptor layer, observed in 4.0, 17.6, 42.9 and 71.4 percent of such mice at 3, 5, 7 and 12 months of age, respectively. Mice with uveoretinitis were shown to have serum IgG antibody reactive by indirect immunofluorescence with retinal photoreceptors, and with interphotoreceptor retinoid-binding protein (IRBP), but not retinal S-antigen, by immunoblotting and ELISA. IRBP is an approximately 140 kDa glycoprotein consisting of about 1260 amino acid residues. We found that residues 1182-1194 is the immunodominant determinant in TG nude mice, and that tryptophan at residue 1182 and proline at residue 1194 are agretopes of the peptide. A uveoretinitis could be adoptively transferred to syngeneic ungrafted nude mice by splenic CD4-positive T cells from diseased animals. This is the first experimental model of a (T-cell mediated) autoimmune uveoretinitis which develops spontaneously and which is not dependent upon deliberate sensitization with retinal antigens and adjuvants.