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B10RIII小鼠中IRBP诱导的实验性自身免疫性葡萄膜视网膜炎中的巨噬细胞和树突状细胞

Macrophages and dendritic cells in IRBP-induced experimental autoimmune uveoretinitis in B10RIII mice.

作者信息

Jiang H R, Lumsden L, Forrester J V

机构信息

Department of Ophthalmology, University of Aberdeen Medical School Foresterhill, Scotland, United Kingdom.

出版信息

Invest Ophthalmol Vis Sci. 1999 Dec;40(13):3177-85.

PMID:10586940
Abstract

PURPOSE

To investigate the characteristics of the mononuclear cell infiltrate in murine experimental autoimmune uveoretinitis (EAU).

METHODS

EAU was induced by immunization with bovine interphotoreceptor retinal binding protein (IRBP) in Freund's complete adjuvant (subcutaneous injection) and pertussis toxin (intraperitoneal injection) in B10RIII mouse. Then animals were killed on days 7, 9, 12, 15, 20, 26, and 39 after immunization. Eyes were processed for hematoxylin and eosin staining to characterize the disease and to assess the severity and extent of the EAU. Single and dual immunohistochemical staining in various combinations with monoclonal antibodies against CD45, CD4, CD8, major histocompatibility complex (MHC) class II, CD11c, NLDC-145, and a variety of macrophage markers was performed.

RESULTS

The authors' results showed that vitritis, vasculitis and perivasculitis, retinal detachment, and granuloma formation in retina and choroid were the predominant features of IRBP-induced B10RIII mice EAU. Immunohistologic results showed that CD4+ T cells and macrophages were the main infiltrating cells in retina and choroid throughout the entire course of the disease. MHC class II negative macrophages expressing antigens reacting with MOMA-2, F4/80, sialoadhesin, and CD11b were prominent during the peak phase of tissue damage in the retina and choroid. Dendritic cells (DCs) characterized by dual positivity for MHC class II and CD11c and negative for sialoadhesin appeared at time of disease onset and continued to be recruited during the inflammatory process. DCs at the site of inflammation were NLDC-145 weak and CD8 negative, indicating that they were of the myeloid rather than the lymphoid lineage.

CONCLUSIONS

The results suggest that EAU in B10RIII mice is initiated by local-infiltrating, dendritic antigen-presenting cells, whereas tissue damage is associated with sialoadhesin-positive, phagocytic nonantigen-presenting macrophages during the effector stage.

摘要

目的

研究小鼠实验性自身免疫性葡萄膜视网膜炎(EAU)中单核细胞浸润的特征。

方法

在B10RIII小鼠中,通过在弗氏完全佐剂(皮下注射)中用牛视网膜色素上皮细胞间视网膜结合蛋白(IRBP)和百日咳毒素(腹腔注射)进行免疫诱导EAU。然后在免疫后第7、9、12、15、20、26和39天处死动物。对眼睛进行苏木精和伊红染色,以表征疾病并评估EAU的严重程度和范围。采用针对CD45、CD4、CD8、主要组织相容性复合体(MHC)II类、CD11c、NLDC-145的单克隆抗体以及多种巨噬细胞标志物进行各种组合的单重和双重免疫组织化学染色。

结果

作者的结果表明,玻璃体炎、血管炎和血管周围炎、视网膜脱离以及视网膜和脉络膜中的肉芽肿形成是IRBP诱导的B10RIII小鼠EAU的主要特征。免疫组织学结果显示,在疾病的整个过程中,CD4 + T细胞和巨噬细胞是视网膜和脉络膜中的主要浸润细胞。在视网膜和脉络膜组织损伤的高峰期,表达与MOMA-2、F4/80、唾液酸粘附素和CD11b反应的抗原的MHC II类阴性巨噬细胞很突出。以MHC II类和CD11c双阳性且唾液酸粘附素阴性为特征的树突状细胞(DCs)在疾病发作时出现,并在炎症过程中持续募集。炎症部位的DCs对NLDC-145呈弱阳性且CD8阴性,表明它们是髓系而非淋巴系来源。

结论

结果表明,B10RIII小鼠的EAU由局部浸润的树突状抗原呈递细胞引发,而在效应阶段,组织损伤与唾液酸粘附素阳性、吞噬性非抗原呈递巨噬细胞有关。

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