The induction of tolerance of renal allografts by adoptive transfer in miniature swine.

The induction of tolerance of renal allografts by adoptive transfer in miniature swine.
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DOI:
10.1111/ajt.12194
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发表时间:
2013-05
期刊:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子:
--
通讯作者:
Yamada K
Yamada K
中科院分区:
其他
文献类型:
--
作者:
Okumi M;Scalea JR;Gillon BC;Tasaki M;Villani V;Cormack T;Hirakata A;Shimizu A;Sachs DH;Yamada K

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我们之前的体外研究数据已经证明,调节机制参与了小型猪I类错配肾移植物的耐受性,小型猪接受了12天的高剂量环孢素A治疗。在本研究中,我们试图通过过继转移长期耐受动物的细胞和/或肾脏来诱导I类错配肾脏的耐受性。15只SLAdd小型猪接受了1.5戈伊全身照射和I类不匹配(SLAgg)的肾脏,这些肾脏来自未处理的猪,有或没有共同移植的肾脏和/或过继转移的细胞来自SLAgg移植物的长期耐受(LTT)SLAdd受体。此外,三只SLAdd小型猪接受了I类错配的肾脏,其中过继转移的细胞来自LTT SLAdd受体。未移植LTT肾的幼稚肾在9天内被排斥。来自LTT动物的幼稚肾沿着细胞和肾移植物的所有受体显示幼稚肾移植物的存活显著延长(第28天、> 150天和> 150天)。这些研究表明,耐受的肾脏具有有效的调节作用,并且来自LTT动物的细胞与肾移植物一起输注增强了这些调节作用。据我们所知,这些研究首次证明了在大型动物中成功的过继性耐受转移。
Our previous in vitro data have demonstrated that regulatory mechanisms are involved in tolerance of class I-mismatched renal allografts in miniature swine treated with 12 days of high dose Cyclsporin A. In the present study, we attempted to induce tolerance of class I-mismatched kidneys by adoptive transfer of cells and/or kidneys from long-term tolerant animals. Fifteen SLAdd miniature swine received 1.5 Gy whole body irradiation and class I-mismatched (SLAgg) kidneys from naïve pigs with or without co-transplanted kidneys and/or adoptively transferred cells from long-term tolerant (LTT) SLAdd recipients of SLAgg grafts. Additionally, three SLAdd miniature swine received class I mismatched kidney with adoptively transferred cells from LTT SLAdd recipients. Naïve kidneys transplanted without a LTT kidney were rejected within 9 days. All recipients of naive kidneys along with cells and kidney grafts from LTT animals showed markedly prolonged survival of the naive renal grafts (day 28, >150 and >150 days). These studies suggest that tolerated kidneys have potent regulatory effects, and cells from LTT animals infused in conjunction with kidney grafts augment these regulatory effects. To our knowledge, these studies represent the first demonstration of successful adoptive transfer of tolerance in large animals.
介导同种异体移植耐受性的FOXP3+ T调节细胞的募集取决于CCR4趋化因子受体。
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