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Ectopic expression of Fas Ligand on cardiomyocytes renders cardiac allografts resistant to CD4(+) T-cell mediated rejection

机译:Fas配体在心肌细胞上的异位表达使心脏同种异体移植抗CD4(+)T细胞介导的排斥反应

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摘要

Fas Ligand limits inflammatory injury and permits allograft survival by inducing apoptosis of Fas-bearing lymphocytes. Previous studies have shown that the CD4(+) T-cell is both sufficient and required for murine cardiac allograft rejection. Here, utilizing a transgenic mouse that over-expresses Fas Ligand specifically on cardiomyocytes as heart donors, we sought to determine if Fas Ligand on graft parenchymal cells could resist CD4(+) T-cell mediated rejection. When transplanted into fully immunocompetent BALB/c recipients Fas Ligand transgenic hearts were acutely rejected. However, when transplanted into CD4(+) T-cell reconstituted BALB/c-rag(-/-) recipients, Fas Ligand hearts demonstrated long-term survival. These results indicate that Fas Ligand over-expression on cardiomyocytes can indeed resist CD4(+) T-cell mediated cardiac rejection and suggests contact dependence between as Ligand expressing graft parenchymal cells and the effector CD4(+) T-cells. (C) 2014 Elsevier Inc. All rights reserved.
机译:Fas配体通过诱导带有Fas的淋巴细胞凋亡来限制炎症损伤并允许同种异体移植物存活。先前的研究表明,CD4(+)T细胞既是鼠心脏同种异体移植排斥反应所必需的。在这里,我们利用转基因小鼠在心脏细胞上过度表达Fas配体作为心脏供体,我们试图确定移植实质细胞上的Fas配体是否可以抵抗CD4(+)T细胞介导的排斥反应。当移植到具有完全免疫能力的BALB / c受体中时,Fas Ligand转基因心脏被急性排斥。但是,当移植到CD4(+)T细胞重建的BALB / c-rag(-/-)受体中时,Fas Ligand心脏表现出长期生存。这些结果表明,Fas配体在心肌细胞上的过度表达确实可以抵抗CD4(+)T细胞介导的心脏排斥反应,并表明配体表达的移植实质细胞与效应CD4(+)T细胞之间的接触依赖性。 (C)2014 Elsevier Inc.保留所有权利。

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