Indoleamine 2,3-dioxygenase expression in trans-planted NOD islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes
Indoleamine 2,3-dioxygenase expression in trans-planted NOD islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes
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DOI：
10.2337/diabetes.51.2.356
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发表时间：
2002-02-01
期刊：
影响因子：
7.7
通讯作者：
Trucco, M
中科院分区：
文献类型：
--
作者：
Alexander, AM;Crawford, M;Trucco, M
吲哚胺2,3-双加氧酶（IDO）催化氨基酸色氨酸分解成犬神经氨酸。研究表明，胎盘滋养细胞产生的IDO可以阻止母体t细胞的攻击，这些t细胞是由胎儿组织表达的父本HLA等位基因激活的。在这篇文章中，我们发现腺病毒基因转移IDO到胰岛可以充分消耗培养基中的色氨酸，从而抑制t细胞的体外增殖。体内实验也表明，将来自糖尿病前期NOD小鼠供体的表达ido的胰岛移植到NOD-scid受体小鼠中，在过继性转移NOD致糖尿病t细胞后，胰岛移植存活时间延长。这种保护是由于肾包膜下移植部位色氨酸的消耗。这些结果表明，局部调节色氨酸分解代谢可能是促进胰岛移植治疗1型糖尿病的一种手段。
Indoleamine 2,3-dioxygenase (IDO) catalyzes the breakdown of the amino acid tryptophan into kyneurenine. It has been shown that IDO production by placental trophoblasts prevents the attack of maternal T-cells activated in response to the paternal HLA alleles expressed by the tissues of the fetus. In this article, we show that adenoviral gene transfer of IDO to pancreatic islets can sufficiently deplete culture media of tryptophan and consequently inhibit the proliferation of T-cells in vitro. Experiments in vivo have also demonstrated that transplantation of IDO-expressing islets from prediabetic NOD mouse donors into NOD-scid recipient mice is associated with a prolongation in islet graft survival after adoptive transfer of NOD diabetogenic T-cells. This protection is attributed to the depletion of tryptophan at the transplantation site beneath the kidney capsule. These results suggest that local modulation of tryptophan catabolism may be a means of facilitating islet transplantation as a therapy for type 1 diabetes.