Role of the thymus in transplantation tolerance in miniature swine: IV. The thymus is required during the induction phase, but not the maintenance phase, of renal allograft tolerance
Role of the thymus in transplantation tolerance in miniature swine: IV. The thymus is required during the induction phase, but not the maintenance phase, of renal allograft tolerance
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DOI：
10.1097/01.tp.0000116416.10799.c6
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发表时间：
2004-04-15
期刊：
影响因子：
6.2
通讯作者：
Yamada, K
中科院分区：
文献类型：
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作者：
Vagefi, PA;Ierino, FL;Yamada, K
背景资料。作者的实验室以前证明，小型猪对I类不同的同种异体肾移植的长期耐受性可以由短程环孢素A(CsA)诱导，并且这种稳定的耐受性依赖于完整胸腺的存在。在本研究中，作者研究了移植前、耐受诱导和维持阶段对胸腺的需求。22只小型猪接受了I类主要组织相容性复合体不相合的肾移植，并接受了12天的CsA疗程。胸腺切除手术时间分别为-21天、0天、+8天、+21天，大于或等于+42天。历史对照包括胸腺切除组和假胸腺切除组。胸腺切除、假胸腺切除和大于或等于+42天的胸腺切除受者肾功能稳定，抗供体细胞毒性T淋巴细胞(CTL)反应最小。相比之下，第21天和第0天的胸腺切除受者表现出同种异体移植物功能障碍、显著的细胞浸润、严重的血管炎和肾小球改变，以及强烈的抗供体CTL反应。+8天和+21天切除胸腺的动物没有发生严重的排斥反应，但同样也没有表现出稳定的临床过程。这些数据表明，在诱导快速和稳定的耐受中，胸腺功能的需求在移植后的前8天是最大的，然后在接下来的2周内减少。+21天后胸腺切除不能影响耐受过程，提示胸腺功能不是维持耐受所必需的。了解胸腺在建立耐受性中的作用可能有助于制定耐受性诱导策略，特别是对于儿科移植受者。
Background. The authors' laboratory previously demonstrated that long-term tolerance to class I-disparate renal allografts in miniature swine can be induced by a short course of cyclosporine A (CsA), and that this stable tolerance is dependent on the presence of an intact thymus. In the present study, the authors have examined the requirement for a thymus during the pretransplant, induction, and maintenance phases of tolerance.Methods. Twenty-two miniature swine underwent class I major histocompatibility complex-mismatched renal transplantation, with a 12-day course of CsA. Thymectomies were performed on days -21, 0, +8, +21, and greater than or equal to +42, in relation to the day of transplantation. Historical controls consisted of euthymic and sham-thymectomized recipients.Results. Euthymic, sham-thymectomized, and day-greater than or equal to +42 thymectomized recipients demonstrated stable renal function and minimal anti-donor cytotoxic T-lymphocyte (CTL) responses. In contrast, day -21 and day 0 thymectomized recipients demonstrated allograft dysfunction, marked cellular infiltrates, with severe vasculitis and glomerular changes, and strong anti-donor CTL responses. Animals thymectomized on days +8 and +21 did not undergo severe rejection, but likewise did not demonstrate a stable clinical course.Conclusions. These data indicate that the requirement for thymic function in the induction of rapid and stable tolerance is greatest during the first 8 days and then diminishes over the next 2 weeks posttransplant. Failure of thymectomy to affect the course of tolerance after day +21 suggests that thymic function is not required for the maintenance of tolerance. Understanding the role of the thymus in establishing tolerance may permit the development of tolerance induction strategies, especially for pediatric transplant recipients.