Ishimoto S, Zhang J, Gullapalli V K, Pararajasegaram G, Rao N A
Doheny Eye Institute and the Department of Ophthalmology, University of Southern California School of Medicine, California, 90033, USA.
Exp Eye Res. 1998 Nov;67(5):539-48. doi: 10.1006/exer.1998.0545.
The present study attempts to identify the antigen-presenting cells in the retina, utilizing bone marrow-transplanted chimeric rats. Two types of chimeras were used: one produced by transplanting bone marrow cells from F1 hybrids of Lewis and Brown Norway (BN) into sublethally irradiated Brown Norway rats (LBN/F1-->BN), followed by adoptive transfer of S-antigen-specific T cells obtained from Lewis rats; the second produced by transplanting bone marrow cells from BN rats into sublethally irradiated F1 hybrids (BN-->LBN/F1), followed by adoptive transfer of S-antigen-specific T cells obtained from F1 hybrids. As controls, Lewis, F1 hybrids and BN rats also received adoptive transfer of syngeneic uveitogenic T cell lines. All animals were killed on the seventh day after adoptive transfer and their eyes and pineal glands were analysed immunohistochemically, utilizing antibody directed against Lewis specific MHC class II molecules(OX-3). The analyses revealed the development of uveoretinitis and pinealitis in both types of chimeras and in the Lewis and F1 hybrid rats. BN rats did not develop uveoretinitis. OX-3-positive cells were found in the retina and the pineal glands of both types of chimeras, and in the Lewis and F1 hybrid rats but not in the BN rats. These cells in the retina expressed dendritic morphology and perivascular distribution. Retinal pigment epithelia, Müller cells and the vascular endothelia of both chimeras, the two strains, and the F1 hybrid rats did not demonstrate OX-3-positive staining. These results suggest that the bone marrow-derived cells in the retina and pineal gland may present S-antigen to T cells, initiating the cascade of uveoretinitis and pinealitis.
本研究试图利用骨髓移植嵌合大鼠来鉴定视网膜中的抗原呈递细胞。使用了两种类型的嵌合体：一种是将Lewis和Brown Norway（BN）的F1杂种的骨髓细胞移植到经亚致死剂量照射的Brown Norway大鼠（LBN/F1→BN）中，随后过继转移从Lewis大鼠获得的S抗原特异性T细胞；另一种是将BN大鼠的骨髓细胞移植到经亚致死剂量照射的F1杂种（BN→LBN/F1）中，随后过继转移从F1杂种获得的S抗原特异性T细胞。作为对照，Lewis、F1杂种和BN大鼠也过继转移了同基因葡萄膜炎致病T细胞系。所有动物在过继转移后第7天处死，利用针对Lewis特异性MHC II类分子（OX-3）的抗体对其眼睛和松果体进行免疫组织化学分析。分析显示，两种类型的嵌合体以及Lewis和F1杂种大鼠均发生了葡萄膜视网膜炎和松果体炎。BN大鼠未发生葡萄膜视网膜炎。在两种类型的嵌合体以及Lewis和F1杂种大鼠的视网膜和松果体中发现了OX-3阳性细胞，但在BN大鼠中未发现。视网膜中的这些细胞表现出树突状形态和血管周围分布。两种嵌合体、两个品系以及F1杂种大鼠的视网膜色素上皮细胞、Müller细胞和血管内皮均未显示OX-3阳性染色。这些结果表明，视网膜和松果体中源自骨髓的细胞可能将S抗原呈递给T细胞，从而引发葡萄膜视网膜炎和松果体炎的级联反应。
