Adoptive Transfer of Renal Allograft Tolerance in a Large Animal Model.
Adoptive Transfer of Renal Allograft Tolerance in a Large Animal Model.
复制标题
DOI：
10.1111/ajt.13424
复制
发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Sachs DH
中科院分区：
文献类型：
--
作者：
Villani V;Yamada K;Scalea JR;Gillon BC;Arn JS;Sekijima M;Tasaki M;Cormack TA;Moran SG;Torabi R;Shimizu A;Sachs DH
我们最近在近交系猪模型中的研究表明，外周和移植物内调节细胞都是将耐受性过继转移到第二个幼稚供体匹配肾脏所必需的。在这里，我们问是否需要外周和移植物内的调节元件过继转移的耐受性时，只有一个长期耐受（LTT）肾移植。9头高度近交系猪接受耐受诱导方案，以制备LTT肾移植物，然后将其移植至组织相容性受体，有或没有过继转移耐受至幼稚肾所需的外周细胞群。与我们以前的研究相反，在没有转移额外的外周细胞和没有增加供体中调节性T细胞的数量/效力的策略的情况下，实现了单独的LTT肾移植的耐受性。这种耐受性是全身性的，因为大多数随后的供体匹配的挑战肾移植被接受。这些结果证实了LTT肾同种异体移植物中存在有效的耐受诱导和/或耐受维持细胞群。他们进一步表明，将耐受性过继转移到幼稚供体匹配的肾脏所需的额外外周耐受机制取决于外周细胞，如果不与LTT肾脏一起转移，则需要时间在过继宿主中发育。
Our recent studies in an inbred swine model demonstrated that both peripheral and intra-graft regulatory cells were required for the adoptive transfer of tolerance to a second, naïve donor-matched kidney. Here, we have asked whether both peripheral and intra-graft regulatory elements are required for adoptive transfer of tolerance when only a long-term tolerant (LTT) kidney is transplanted. Nine highly-inbred swine underwent a tolerance-inducing regimen to prepare LTT kidney grafts which were then transplanted to histocompatible recipients, with or without the peripheral cell populations required for adoptive transfer of tolerance to a naïve kidney. In contrast to our previous studies, tolerance of the LTT kidney transplants alone was achieved without transfer of additional peripheral cells and without strategies to increase the number/potency of regulatory T cells in the donor. This tolerance was systemic, since most subsequent, donor-matched challenge kidney grafts were accepted. These results confirm the presence of a potent tolerance-inducing and/or tolerance-maintaining cell population within LTT renal allografts. They suggest further that additional peripheral tolerance mechanisms, required for adoptive transfer of tolerance to a naïve donor-matched kidney, depend on peripheral cells that, if not transferred with the LTT kidney, require time to develop in the adoptive host.