CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival
CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival
复制标题
DOI：
10.1172/jci119173
复制
发表时间：
1997-02-01
影响因子：
15.9
通讯作者：
Ferguson, TA
中科院分区：
文献类型：
--
作者：
Stuart, PM;Griffith, TS;Ferguson, TA
尽管解剖屏障和可溶性介质与免疫赦免有关，但组织相关CD 95配体（Fas ligand，Fast）引起的Fas（+）细胞凋亡似乎是免疫赦免的重要组成部分。免疫特权位点功能的一个临床实例是人类角膜移植的成功，其中非常高百分比的移植接受没有组织匹配或免疫抑制治疗。由于小鼠角膜表达丰富的Fas配体和免疫赦免已被牵连在这些移植的成功，我们检查的作用，快速在角膜移植我们的结果表明，人角膜表达功能性的快速能够杀死Fas（+）淋巴细胞在体外培养系统。使用小鼠模型进行角膜同种异体移植，FasL（+）角膜移植物的接受率为45%，而FasL（-）移植物或移植到Fas（-）小鼠的正常移植物的排斥率为100%。组织学分析发现，FasL（+）移植物含有凋亡的单核细胞，表明移植物诱导凋亡，而排斥FasL（-）角膜含有大量炎性细胞，无相关凋亡。总之，我们的结果表明，角膜上的快速表达是角膜移植物存活的主要因素，因此，我们为人类最成功的组织移植之一提供了解释。
Although anatomical barriers and soluble mediators have been implicated in immune privilege, it appears that the apoptotic cell death of Fas(+) cells by tissue-associated CD95 ligand (Fas ligand, Fast) is an important component. One clinical example of the function of an immune privileged site is the success of human corneal transplants, where a very high percentage of transplants accept without tissue matching or immunosuppressive therapy. Since the mouse cornea expresses abundant Fas ligand and immune privilege has been implicated in the success of these transplants, we examined the role of Fast in corneal transplantation Our results show that human corneas express functional Fast capable of killing Fas(+) lymphoid cells in an in vitro culture system. Using a mouse model for corneal allograft transplantation, FasL(+) orthografts were accepted at a rate of 45%, whereas FasL(-) grafts, or normal grafts transplanted to Fas(-) mice, were rejected 100% of the time. Histological analysis found that FasL(+) grafts contained apoptotic mononuclear cells indicating the induction of apoptosis by the graft, while rejecting FasL(-) corneas contained numerous inflammatory cells without associated apoptosis. Taken together our results demonstrate that Fast expression on the cornea is a major factor in corneal allograft survival and, thus, we provide an explanation for one of the most successful tissue transplants performed in humans.