Zhang Er-Ping, Müller Anja, Ignatius Ralf, Hoffmann Friedrich
Department of Ophthalmology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany.
Transplantation. 2003 Nov 27;76(10):1511-3. doi: 10.1097/01.TP.0000086344.04487.4F.
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.
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.
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.
FTY720 treatment substantially protects corneal allografts and may provide an immunomodulatory strategy in clinical corneal transplantation.
新型免疫调节剂FTY720主要通过将淋巴细胞隔离至二级淋巴组织发挥作用，从而抑制其浸润至移植器官。本研究旨在探讨其对角膜移植存活的影响。
16只BALB/c小鼠（H-2d）接受来自C3H（H-2k）小鼠的角膜移植。8只小鼠从第-1天至第11天每天口服FTY720（10mg/kg），所有动物同时接受0.1%地塞米松滴眼液治疗。此外，对经过类似处理的动物的眼睛和局部淋巴结进行免疫组织化学和增殖分析。
FTY720显著延长移植物存活时间，从28±8.1天延长至36.5±7.1天（P=0.021）。在接受治疗的动物中，CD4+和F4/80+细胞的角膜浸润分别从70.8±60.3降至7.0±9.0（P=0.004）和从97.5±30.7降至44.8±24.9（P=0.01），同种异体T细胞增殖减少。
FTY720治疗可显著保护角膜同种异体移植物，并可能为临床角膜移植提供一种免疫调节策略。
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