Department of Anatomy and Physiology, School of Biomedical Sciences (D.D., J.L.W.-B.), University of Melbourne, Parkville, Victoria, Australia.
Department of Diabetes, Monash University, Melbourne, Victoria, Australia (D.D., J.L.W.-B.).
Arterioscler Thromb Vasc Biol. 2023 Apr;43(4):522-536. doi: 10.1161/ATVBAHA.122.318079. Epub 2023 Feb 16.
CD4 (cluster of differentation) and CD8 T cells are increased in the ocular fluids of patients with neovascular retinopathy, yet their role in the disease process is unknown.
We describe how CD8 T cells migrate into the retina and contribute to pathological angiogenesis by releasing cytokines and cytotoxic factors.
In oxygen-induced retinopathy, flow cytometry revealed the numbers of CD4 and CD8 T cells were increased in blood, lymphoid organs, and retina throughout the development of neovascular retinopathy. Interestingly, the depletion of CD8 T cells but not CD4 T cells reduced retinal neovascularization and vascular leakage. Using reporter mice expressing gfp (green fluorescence protein) in CD8 T cells, these cells were localized near neovascular tufts in the retina, confirming that CD8 T cells contribute to the disease. Furthermore, the adoptive transfer of CD8 T cells deficient in TNF (tumor necrosis factor), IFNγ (interferon gamma), Prf (perforin), or GzmA/B (granzymes A/B) into immunocompetent mice revealed that CD8 T cells mediate retinal vascular disease via these factors, with TNF influencing all aspects of vascular pathology. The pathway by which CD8 T cells migrate into the retina was identified as CXCR3 (C-X-C motif chemokine receptor 3) with the CXCR3 blockade reducing the number of CD8 T cells within the retina and retinal vascular disease.
We discovered that CXCR3 is central to the migration of CD8 T cells into the retina as the CXCR3 blockade reduced the number of CD8 T cells within the retina and vasculopathy. This research identified an unappreciated role for CD8 T cells in retinal inflammation and vascular disease. Reducing CD8 T cells via their inflammatory and recruitment pathways is a potential treatment for neovascular retinopathies.
患有新生血管性视网膜病变的患者的眼液中 CD4（分化簇）和 CD8 T 细胞增加，但它们在疾病过程中的作用尚不清楚。
我们描述了 CD8 T 细胞如何通过释放细胞因子和细胞毒性因子迁移到视网膜并促进病理性血管生成。
在氧诱导的视网膜病变中，流式细胞术显示 CD4 和 CD8 T 细胞的数量在整个新生血管性视网膜病变的发展过程中在血液、淋巴器官和视网膜中增加。有趣的是，耗尽 CD8 T 细胞而不是 CD4 T 细胞可减少视网膜新生血管形成和血管渗漏。使用在 CD8 T 细胞中表达 GFP（绿色荧光蛋白）的报告小鼠，这些细胞定位于视网膜中新生血管丛附近，证实 CD8 T 细胞有助于疾病的发生。此外，将缺乏 TNF（肿瘤坏死因子）、IFNγ（干扰素 γ）、Prf（穿孔素）或 GzmA/B（颗粒酶 A/B）的 CD8 T 细胞过继转移到免疫功能正常的小鼠中，揭示了 CD8 T 细胞通过这些因子介导视网膜血管疾病，其中 TNF 影响血管病理学的各个方面。鉴定出 CD8 T 细胞迁移到视网膜的途径是 CXCR3（C-X-C 基序趋化因子受体 3），CXCR3 阻断减少了视网膜内的 CD8 T 细胞数量和视网膜血管疾病。
我们发现 CXCR3 是 CD8 T 细胞迁移到视网膜的核心，因为 CXCR3 阻断减少了视网膜内的 CD8 T 细胞数量和血管病变。这项研究确定了 CD8 T 细胞在视网膜炎症和血管疾病中的未被认识的作用。通过其炎症和募集途径减少 CD8 T 细胞是治疗新生血管性视网膜病变的一种潜在方法。
