Retina-specific T regulatory cells bring about resolution and maintain remission of autoimmune uveitis.
Retina-specific T regulatory cells bring about resolution and maintain remission of autoimmune uveitis.
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DOI：
10.4049/jimmunol.1402650
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发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Caspi RR
中科院分区：
文献类型：
--
作者：
Silver PB;Horai R;Chen J;Jittayasothorn Y;Chan CC;Villasmil R;Kesen MR;Caspi RR
通过用视网膜抗原 IRBP 免疫小鼠诱导的实验性自身免疫性葡萄膜炎 (EAU) 是人类自身免疫性葡萄膜炎的模型。我们检查了葡萄膜眼中发现的 T 调节 (Treg) 细胞是否 (i) IRBP 特异性，(ii) 功能抑制，以及 (iii) 在疾病自然消退和维持缓解中发挥作用。葡萄膜炎眼中 Foxp3+ Treg 与 T 效应子 (Teff) 比率的逐渐增加与疾病的缓解相关。在疾病高峰期，高达 20% 的 Treg (CD4+Foxp3+) 和高达 60% 的 Teff (CD4+FoxP3−) 细胞具有 IRBP 特异性，而在淋巴器官中无法检测到视网膜特异性 T 细胞。从患有 EAU 的小鼠眼睛中分离出的 Tregs 有效地抑制了来自同一眼睛的 Teff 的 IRBP 特异性反应。重要的是，疾病高峰期Tregs的系统性耗竭延迟了EAU的消退，消退后Tregs的耗竭引发了复发。这可以通过眼内局部 Tregs 的消耗来部分重复。因此，具有多克隆 T 细胞库的正常小鼠葡萄膜眼中浸润的 T 细胞高度富集 IRBP 特异性 Treg 和 Teff 细胞。与其他炎症部位的 Tregs 报道不同，葡萄膜炎眼的 Tregs 似乎功能未受损。最后，Foxp3+ Tregs 在葡萄膜炎的自然消退和维持缓解中发挥作用，这至少部分是通过眼睛局部的作用发生的。
Experimental autoimmune uveitis (EAU) induced in mice by immunization with the retinal antigen IRBP is a model of human autoimmune uveitis. We examined whether T regulatory (Treg) cells found in uveitic eyes are (i) IRBP specific, (ii) functionally suppressive, and (iii) play a role in natural resolution of disease and in maintenance of remission. Progressive increase of Foxp3+ Treg to T effector (Teff) ratio in uveitic eyes correlated with resolution of disease. At peak disease, up to 20% of Treg (CD4+Foxp3+) and up to 60% of Teff (CD4+FoxP3−) cells were IRBP-specific, while in lymphoid organs retina-specific T cells were undetectable. Tregs isolated from eyes of mice with EAU efficiently suppressed IRBP-specific responses of Teff from the same eyes. Importantly, systemic depletion of Tregs at peak disease delayed resolution of EAU, and their depletion after resolution triggered a relapse. This could be partially duplicated by depletion of Tregs locally within the eye. Thus, the T cell infiltrate in uveitic eyes of normal mice with a polyclonal T cell repertoire is highly enriched in IRBP-specific Treg and Teff cells. Unlike what has been reported for Tregs in other inflammatory sites, Tregs from uveitic eyes appear unimpaired functionally. Finally, Foxp3+ Tregs play a role in the natural resolution of uveitis and in the maintenance of remission, which occurs at least in part through an effect that is local to the eye.
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