Xenogeneic thymus transplantation in a pig-to-baboon model.
Xenogeneic thymus transplantation in a pig-to-baboon model.
复制标题
猪狒狒模型中的异种胸腺移植。
DOI：
10.1097/01.tp.0000044137.97841.99
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发表时间：
2003
期刊：
影响因子：
6.2
通讯作者：
Sachs,DavidH
中科院分区：
文献类型：
--
作者：
Wu,Anette;Yamada,Kazuhiko;Neville,DavidM;Awwad,Michel;Wain,JohnC;Shimizu,Akira;Gojo,Satoshi;Kitamura,Hiroshi;Colvin,RobertB;Cooper,DavidKC;Sykes,Megan;Sachs,DavidH
背景。我们测试了胎儿猪胸腺组织移植是否能在不一致的（猪-狒狒）异种屏障中产生耐受性。方法：6只狒狒接受胸腺切除术、脾切除术和结合白喉毒素结合位点突变体（FN18-CRM9）的抗猴CD3抗体的调节方案。将猪胎儿或新生儿胸腺组织移植到三只狒狒体内。3只对照狒狒接受未移植猪组织（n= 1）或成年猪淋巴结（n= 2）。结果：实验狒狒经t细胞清除和胸腺移植后，胸腺依赖性naïve-type CD4细胞（CD4/CD45RA高）恢复，体外异种性低反应。未观察到α -半乳糖抗体反应致敏。胸腺移植物存活了48天。在其中两只动物中进行了猪皮异种移植，存活时间分别为22天和24天。对照狒狒：这些动物中只有两只T细胞完全耗尽，并且都未能恢复胸腺依赖性T细胞（CD4/CD45RA高）。在一只动物中，观察到普遍的体外反应性低下，随后死于感染。第二只动物在体外表现出T细胞恢复延迟和长时间的一般低反应性。与同种异体移植相比，两种动物都没有表现出猪皮肤移植的延长（均在第13天出现排斥）。猪胸腺组织能够诱导异种低反应性。更有效的胸腺移植可能允许这种方法诱导异种移植物耐受。
Background.We have tested whether fetal porcine thymic tissue transplantation can lead to tolerance across a discordant (pig-to-baboon) xenogeneic barrier.Methods.Six baboons underwent a conditioning regimen with thymectomy, splenectomy, and anti-monkey CD3 antibody conjugated to a diphtheria toxin binding site mutant (FN18-CRM9). Porcine fetal or neonatal thymic tissue was transplanted into three baboons. Three control baboons received either no transplanted pig tissue (n= 1) or adult pig lymph node (n= 2). Cellular responses and skin xenografts were used to test for tolerance.Results.Experimental baboons: After T-cell depletion and thymic transplantation, recovery of thymus-dependent naïve-type CD4 cells (CD4/CD45RA high) and in vitro xenogeneic hyporesponsiveness were observed. No sensitization of alpha-galactosyl antibody responses was observed. The thymic grafts survived up to 48 days. Porcine skin xenografts were performed in two of these animals with survival of 22 and 24 days. Control baboons: Only two of these animals were completely T-cell depleted, and both failed to recover thymus-dependent T cells (CD4/CD45RA high). In one animal, general in vitro hyporesponsiveness was observed, with subsequent death from infection. The second animal demonstrated delayed recovery of T cells and prolonged general hyporesponsiveness in vitro. Neither animal demonstrated prolongation of porcine skin grafts compared with allografts (both rejected by day 13).Conclusions.Porcine thymic tissue is able to induce xenogeneic hyporesponsiveness. More efficient thymic engraftment may allow this approach to induce xenograft tolerance.