Vascularized thymic lobe transplantation in miniature swine: Thymopoiesis and tolerance induction across fully MHC-mismatched barriers
Vascularized thymic lobe transplantation in miniature swine: Thymopoiesis and tolerance induction across fully MHC-mismatched barriers
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DOI：
10.1073/pnas.0306666101
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发表时间：
2004-03-16
影响因子：
11.1
通讯作者：
Yamada, K
中科院分区：
文献类型：
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作者：
Kamano, C;Vagefi, PA;Yamada, K
作为免疫系统中自我与非自我辨别的主要部位，胸腺如果成功移植，可能会对来自同一供体的任何其他器官或组织产生中枢耐受性。我们最近开发了一种技术，移植一个完整的，血管化的胸腺叶（胸腺）在小型猪。在本研究中，我们研究了这种同种异体移植物支持胸腺生成和诱导移植耐受的能力，通过完全MHC不匹配的障碍。六个小型猪受体接受了完全MHC不匹配的自体移植物，并接受了12天的他克莫司治疗。其中3例受者在移植前切除胸腺，并长期接受同种异体胸腺移植，有正常胸腺生成的证据。与此相反，三个正常的受体排斥他们的同种异体肾移植。供体肾移植，匹配的供体肾移植，移植到两个胸腺切除的三个受体，和一个正常的胸腺受体，没有免疫抑制剂。这些肾移植物被胸腺切除的受体接受，但被胸腺正常的受体以加速的方式排斥。因此，这项研究表明，成功移植的血管化胸腺跨越完全MHC不匹配的屏障诱导耐受性，在这个临床前，大动物模型。这一过程将使研究胸腺在移植免疫学中的作用成为可能，并为临床移植中诱导耐受提供一种潜在的策略。
As the major site of self-nonself discrimination in the immune system, the thymus, if successfully transplanted, could potentially carry with it the induction of central tolerance to any other organ or tissue from the same donor. We have recently developed a technique for transplantation of an intact, vascularized thymic lobe (VTL) in miniature swine. In the present study, we have examined the ability of such VTL allografts to support thymopoiesis and induce transplantation tolerance across fully MHC-mismatched barriers. Six miniature swine recipients received fully MHC-mismatched VTL grafts with a 12-day course of tacrolimus. Three of these recipients were thymectomized before transplantation and accepted their VTL allografts long-term, with evidence of normal thymopoiesis. In contrast, three euthymic recipients rejected their VTL allografts. Donor renal allografts, matched to the donor VTL grafts, were transplanted without immunosuppression into two of the three thymectomized recipients, and one of the three euthymic recipients. These renal allografts were accepted by thymectomized recipients, but rejected by the euthymic recipient in an accelerated fashion. This study thus demonstrates that successful transplantation of a vascularized thymus across a fully MHC-mismatched barrier induces tolerance in this preclinical, large-animal model. This procedure should enable studies on the role of the thymus in transplantation immunology as well as offer a potential strategy for tolerance induction in clinical transplantation.