Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Department of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Department of Ophthalmology, Erasmus Medical Center Rotterdam, Doctor Molewaterplein 50-60, 3015 GJ Rotterdam, The Netherlands.
Hum Immunol. 2014 Jun;75(6):570-7. doi: 10.1016/j.humimm.2014.02.012. Epub 2014 Feb 12.
Birdshot chorioretinopathy (BSCR), a progressive form of non-infectious uveitis, is the strongest HLA-associated disease described to date, with >95% of the patients displaying HLA-A29. Since indirect evidence indicates the involvement of T cells in the etiopathology of the disease, we now isolated, cultured and analyzed the vitreous fluid-infiltrating T cells from two BSCR patients with respect to their phenotype, cytokine profile, clonal distribution and antigen specificity. Phenotypic analyses revealed the predominant presence of both CD4(+) and CD8(+) T cells in vitreous fluid. Further analyses on short term expanded and cloned T cells suggested that eye-infiltrating T cells generally displayed a Th1 like cytokine profile with secretion of high levels of IFN-γ and TNF-α. In one patient an oligoclonal CD4(+) and CD8(+) T cell infiltration, with a moderate to strongly skewed TCR Vβ usage was suggestive for an antigen driven infiltration/expansion. Indeed, a number of intraocular CD4(+) and CD8(+) T cells responded to crude retinal and choroidal lysates. These results, which demonstrate for the first time the existence of eye-antigen-specific T cells in the vitreous fluid of BSCR patients, substantiate the current view on the role of eye-antigen specific T cells in the etiopathology of BSCR.
鸟枪弹样脉络膜视网膜病变（BSCR）是一种进行性非传染性葡萄膜炎，是迄今为止与 HLA 相关性最强的疾病，>95%的患者显示 HLA-A29。由于间接证据表明 T 细胞参与了疾病的病因发病机制，我们现在从两名 BSCR 患者的玻璃体液中分离、培养和分析了浸润性 T 细胞，以研究其表型、细胞因子谱、克隆分布和抗原特异性。表型分析显示玻璃体液中主要存在 CD4(+)和 CD8(+)T 细胞。对短期扩增和克隆的 T 细胞的进一步分析表明，眼内浸润 T 细胞通常表现出 Th1 样细胞因子谱，分泌高水平的 IFN-γ和 TNF-α。在一名患者中，中等至强烈偏向 TCR Vβ 使用的寡克隆 CD4(+)和 CD8(+)T 细胞浸润提示抗原驱动的浸润/扩增。事实上，一些眼内 CD4(+)和 CD8(+)T 细胞对粗制视网膜和脉络膜裂解物有反应。这些结果首次证明了 BSCR 患者玻璃体液中存在眼抗原特异性 T 细胞，证实了目前关于眼抗原特异性 T 细胞在 BSCR 病因发病机制中的作用的观点。
