Thymic transplantation in miniature swine. III. Induction of tolerance by transplantation of composite thymokidneys across fully major histocompatibility complex-mismatched barriers
Thymic transplantation in miniature swine. III. Induction of tolerance by transplantation of composite thymokidneys across fully major histocompatibility complex-mismatched barriers
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DOI：
10.1097/01.tp.0000080608.42480.e8
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发表时间：
2003-08-15
期刊：
影响因子：
6.2
通讯作者：
Sachs, DH
中科院分区：
文献类型：
--
作者：
Yamada, K;Vagefi, PA;Sachs, DH
背景。本研究确定了在移植前将自体胸腺组织植入供体肾包膜下制备的复合胸腺肾（TK）移植物是否能诱导幼年agh -微型猪跨双单倍型全主要组织相容性复合体（MHC）错配屏障的同种异体移植耐受。在移植前2 ~ 3个月，将自体胸腺组织植入供体动物肾包膜下制备TK移植物。4名受者接受t细胞消耗免疫毒素治疗，并接受完全不匹配的amc TK移植物加上12天的环孢素a （CsA）疗程。对照动物单独或同时给予CsA和免疫毒素治疗，但给予正常肾脏或植入自体淋巴结而非胸腺的肾脏。通过血浆肌酐水平和组织学分析评估移植肾功能。通过细胞介导的淋巴溶解试验监测免疫状态。所有四名接受免疫毒素和12天CsA治疗的完全amc错配TK移植的受者都接受了长期的复合肾异体移植。所有单独接受TK和CsA的对照受体、正常肾脏或含有淋巴结组织的复合肾脏均急性排斥移植物。据我们所知，这是首次在大型动物模型中证明功能性血管化胸腺移植物可以诱导移植耐受完全mhc错配屏障。
Background. This study determines whether composite thymokidney (TK) grafts, created by implantation of autologous thymic tissue beneath the donor's renal capsule before transplantation, could induce allogeneic transplantation tolerance across two-haplotype fully major histocompatibility complex (MHC)mismatched barriers in juvenile AGH-miniature swine.Methods. TK grafts were prepared by implanting autologous thymic tissue under the renal capsule of donor animals 2 to 3 months before transplantation. Four recipients were treated with a T-cell-depleting immunotoxin and received fully AMC-mismatched TK grafts plus a 12-day course of cyclosporine A (CsA). Control animals were treated with CsA alone or both CsA and immunotoxin, but with a normal kidney or a kidney implanted with autologous lymph node rather than thymus. Renal graft function was assessed by plasma creatinine levels and histologic analyses. Immunologic status was monitored by cell-mediated lympholysis assays.Results. All four recipients of fully AMC-mismatched TK transplants treated with immunotoxin and a 12-day course of CsA accepted their composite renal allografts long-term. All control recipients receiving a TK and CsA alone, a normal kidney or a composite kidney containing lymph node tissue acutely rejected their grafts.Conclusions. To our knowledge, this is the first demonstration that functional vascularized thymic grafts can induce transplantation tolerance across fully MHC-mismatched barriers in a large animal model.