Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts
Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts
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DOI：
10.1073/pnas.94.8.3943
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Vaux, DL
中科院分区：
文献类型：
--
作者：
Allison, J;Georgiou, HM;Vaux, DL
CD95 （Fas/APO-1）与其配体（CD95L）结合通常会诱导细胞凋亡。在啮齿类动物睾丸中，CD95L表达诱导的活化T细胞凋亡被认为是免疫特权的机制[Bellgrau， D., Gold， D., Selawry， H., Moore， J., Franzusoff， A. & Duke， R. C. (1995) Nature (London) 377, 630-632]。为了验证CD95L是否能保护胰岛移植物免受排斥反应的影响，我们制作了在胰岛β细胞上表达小鼠CD95L的转基因小鼠，并将胚胎胰腺移植到异体动物肾囊下。CD95L的表达不能保护移植物免受排斥。然而，转基因小鼠胰腺出现粒细胞浸润。这些结果证明了CD95L的促炎功能，并提示CD95L的表达可能不足以保护器官移植物。
Binding of CD95 (Fas/APO-1) by its ligand (CD95L) commonly induces apoptosis. Apoptosis of activated T cells, induced by CD95L expressed in the rodent testis, has been proposed to be the mechanism of immune privilege [Bellgrau, D., Gold, D., Selawry, H., Moore, J., Franzusoff, A. & Duke, R. C. (1995) Nature (London) 377, 630-632]. To test whether CD95L could protect pancreatic islet grafts from rejection, we made transgenic mice expressing murine CD95L on their islet beta cells and transplanted fetal pancreata under the kidney capsules of allogeneic animals. Expression of CD95L failed to protect the grafts from rejection. However, transgenic mice developed a granulocytic infiltration in their pancreata. These results demonstrate a pro-inflammatory function of CD95L and suggest that expression of CD95L may not be sufficient to protect organ allografts.