Thymic transplantation in miniature swine. II. Induction of tolerance by transplantation of composite thymokidneys to thymectomized recipients
Thymic transplantation in miniature swine. II. Induction of tolerance by transplantation of composite thymokidneys to thymectomized recipients
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DOI：
10.4049/jimmunol.164.6.3079
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发表时间：
2000-03-15
影响因子：
4.4
通讯作者：
Sachs, DH
中科院分区：
文献类型：
--
作者：
Yamada, K;Shimizu, A;Sachs, DH
我们实验室以前的研究表明，胸腺的存在对于同种异体移植模型中快速而稳定的耐受诱导是必不可少的。我们现在报告了一种尝试通过在胸腺切除的受者中同时移植供体胸腺移植物和肾脏来诱导对同种异体肾移植的耐受性。受者在接受I类不相合供者的器官和/或组织前3wk接受胸腺切除。受者接受1)单独的同种异体肾移植，2)复合同种异体胸腺肾(包膜下有带血管的自体胸腺组织的肾)，或3)来自同一供者的分离的肾和胸腺移植物。所有受者都接受了12天的环孢素治疗，单独接受同种异体肾移植或单独接受胸腺和肾移植的胸腺切除动物由于严重排斥反应而肾功能不稳定，并持续存在抗供体细胞毒性T细胞反应，相比之下，复合胸腺肾移植受者肾功能稳定，组织学上没有排斥反应的证据，也没有供体特异性无反应。术后第14天，胸腺肾内的胸腺组织含有受体型树突状细胞。术后60d，胸腺髓质内出现受体I类阳性胸腺细胞，提示胸腺生成，T细胞既受MHC限制，又受供者MHC限制。这些数据表明，在胸腺切除的受者中，带血管的供者胸腺组织的存在诱导了对I类不同的肾移植的快速和稳定的耐受。据我们所知，这是功能血管胸腺移植物能够在大型动物模型中诱导移植耐受的第一个证据。
Previous studies in our laboratory have demonstrated that the presence of the thymus is essential for rapid and stable tolerance induction in allotransplant models. We now report an attempt to induce tolerance to kidney allografts by transplanting donor thymic grafts simultaneously with the kidney in thymectomized recipients. Recipients were thymectomized 3 wk before receiving an organ and/or tissues from a class I-mismatched donor. Recipients received 1) a kidney allograft alone, 2) a composite allogeneic thymokidney (kidney with vascularized autologous thymic tissue under its capsule), or 3) separate kidney and thymic grafts from the same donor. All recipients received a 12-day course of cyclosporine, Thymectomized animals receiving a kidney allograft alone or receiving separate thymic and kidney grafts had unstable renal function due to severe rejection with the persistence of anti-donor cytotoxic T cell reactivity, In contrast, recipients of composite thymokidney grafts had stable renal function with no evidence of rejection histologically and donor-specific unresponsiveness. By postoperative day 14, the thymic tissue in the thymokidney contained recipient-type dendritic cells. By postoperative day 60, recipient-type class I positive thymocytes appeared in the thymic medulla, indicating thymopoiesis, T cells were both recipient and donor MHC-restricted. These data demonstrate that the presence of vascularized-donor thymic tissue induces rapid and stable tolerance to class I- disparate kidney allografts in thymectomized recipients. To our knowledge, this is the first evidence of functional vascularized thymic grafts permitting transplantation tolerance to be induced in a large animal model.