研究动态
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CD8+ T细胞在眼部新血管疾病中促进病理性血管生成。

CD8+ T Cells Promote Pathological Angiogenesis in Ocular Neovascular Disease.

发表日期:2023 Feb 16
作者: Devy Deliyanti, William A Figgett, Thomas Gebhardt, Joseph A Trapani, Fabienne Mackay, Jennifer L Wilkinson-Berka
来源: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

摘要:

CD4+和CD8+ T细胞在新生血管性视网膜病患者的眼内液中增加,但它们在疾病过程中的作用仍未知。我们描述了CD8+ T细胞如何移行到视网膜并通过释放细胞因子和细胞毒素因子对病理性血管生成做出贡献。在氧诱导性视网膜病中,流式细胞术显示,在新生血管性视网膜病的发展过程中,CD4+和CD8+ T细胞的数量都增加了。有趣的是,CD8+ T细胞的耗竭而不是CD4+ T细胞可以减少视网膜新生血管和血管渗漏。使用在CD8+ T细胞中表达gfp(绿色荧光蛋白)的记者小鼠,这些细胞定位在视网膜中的新生血管丛附近,证实了CD8+ T细胞对疾病的贡献。此外,将缺乏TNF(肿瘤坏死因子)、IFNγ(干扰素γ)、Prf(穿孔素)或GzmA/B(酶A/B)的CD8+ T细胞移植到免疫能力全技术Rag1-/-小鼠体内,发现CD8+ T细胞通过这些因素介导视网膜血管疾病,TNF影响了血管病理的所有方面。CD8+ T细胞进入视网膜的路径被确定为CXCR3,CXCR3阻断减少了视网膜内CD8+ T细胞和视网膜血管疾病的数量。我们发现,CD8+ T细胞在视网膜炎症和血管疾病中有着被低估的作用。通过减少它们的炎症和招募通路,可以成为新生血管性视网膜病的潜在治疗方法。
CD4+ 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 Rag1-/- 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 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.