Significant prolongation of orthotopic corneal-graft survival in FTY720-treated mice.
Significant prolongation of orthotopic corneal-graft survival in FTY720-treated mice.
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DOI：
10.1097/01.tp.0000086344.04487.4f
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发表时间：
2003-05
期刊：
影响因子：
6.2
通讯作者：
E. Zhang;A. Müller;R. Ignatius;F. Hoffmann
中科院分区：
文献类型：
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作者：
E. Zhang;A. Müller;R. Ignatius;F. Hoffmann
背景资料。新型免疫调节剂FTY720主要通过将淋巴细胞隔离到次级淋巴组织来发挥作用，从而抑制它们对移植器官的渗透。本研究旨在探讨其对角膜移植物存活的影响。方法：研究方法。16只BALB/c小鼠(H-2d)接受C3H(H-2k)小鼠的角膜移植。8只小鼠于−第1~11天灌胃FTY720(10 mg/(kg·d))，同时给予0.1%地塞米松滴眼液。此外，对类似处理的动物的眼睛和区域淋巴结进行了免疫组织化学和增殖分析。结果。FTY720可显著延长移植物存活时间，从28±8.1d延长至36.5d±7.1d(P=0.021)。治疗组外周血中CD_4~+细胞和F4/80~+细胞的角膜浸润率分别从70·8±60·3下降到7·0±9·0(P=0.004)，从97·5±30·7下降到44·8±24·9(P=0·01)，同种异体T细胞增殖减少。结论。FTY720治疗可有效保护同种异体角膜移植物，并可能为临床角膜移植提供一种免疫调节策略。
Background. The novel immunomodulator, FTY720, mainly acts through sequestering of lymphocytes to secondary lymphatic tissue, thereby suppressing their infiltration into grafted organs. This study aimed to investigate its influence on corneal-graft survival. Methods. Sixteen BALB/c mice (H-2d) received corneal transplants from C3H (H-2k) mice. Eight mice were treated with FTY720 (10 mg/kg per day) orally from day −1 to day 11, and all animals received 0.1% dexamethasone eye drops for the same time. In addition, eyes and regional lymph nodes from similarly treated animals were subjected to immunohistochemistry and proliferation assays. Results. FTY720 significantly prolonged graft survival from 28±8.1 to 36.5±7.1 days (P =0.021). In treated animals, corneal infiltration by CD4+ and F4/80+ cells was reduced from 70.8±60.3 to 7.0±9.0 (P =0.004) and from 97.5±30.7 to 44.8±24.9 (P =0.01) cells, respectively, and allogeneic T-cell proliferation was decreased. Conclusions. FTY720 treatment substantially protects corneal allografts and may provide an immunomodulatory strategy in clinical corneal transplantation.