Dullforce Per A, Garman Kiera L, Seitz Greg W, Fleischmann Ross J, Crespo Sergio M, Planck Stephen R, Parker David C, Rosenbaum James T
Department of Ophthalmology at Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.
J Immunol. 2004 Jun 1;172(11):6701-8. doi: 10.4049/jimmunol.172.11.6701.
The migration of APCs from sites of infection and their maturation are critical elements in the generation of immune responses. However, the paths by which intraocular Ags migrate to draining lymph nodes are not known because the eye has limited lymphatic vessels. To date, only dendritic cells from the cornea and conjunctiva have been shown to emigrate. We demonstrate that phagocytic APCs in the anterior uveal tissues of the murine eye that ingest fluorescent latex beads do not migrate to regional lymph nodes. The beads are ingested in the uveal tract by cells expressing MHC class II, CD11c, or F4/80. Using intravital time-lapse videomicroscopy to monitor iris APC migration after anterior chamber injection of fluorescent Ag, fluorescently labeled APCs fail to move at multiple observation times, even in the presence of Ag and LPS. Whereas an as yet unidentified ocular nonphagocytic APC subset might migrate from the anterior uveal tissues, it is more probable that immune responses in the draining lymph nodes are engendered by soluble Ag escaping the eye through interstitial spaces. The inability of anterior uveal tissue APCs to migrate to lymph nodes may contribute to deviant immune responses that dominate after Ags are introduced into the anterior chamber.
抗原呈递细胞(APCs)从感染部位的迁移及其成熟是免疫反应产生的关键因素。然而,由于眼部淋巴管有限,眼内抗原迁移至引流淋巴结的途径尚不清楚。迄今为止,仅角膜和结膜的树突状细胞已被证明会迁移。我们证明,摄取荧光乳胶珠的小鼠眼前葡萄膜组织中的吞噬性APCs不会迁移至局部淋巴结。这些珠子在葡萄膜中被表达MHC II类、CD11c或F4/80的细胞摄取。使用活体延时视频显微镜监测前房注射荧光抗原后虹膜APCs的迁移,即使存在抗原和脂多糖(LPS),在多个观察时间点,荧光标记的APCs仍无法移动。虽然可能存在尚未确定的眼部非吞噬性APCs亚群从眼前葡萄膜组织迁移,但更有可能的是,引流淋巴结中的免疫反应是由通过间隙从眼内逸出的可溶性抗原引发的。眼前葡萄膜组织APCs无法迁移至淋巴结可能导致在抗原被引入前房后占主导地位的异常免疫反应。