Abrogation of renal allograft tolerance in MGH miniature swine: the role of intra-graft and peripheral factors in long-term tolerance.
Abrogation of renal allograft tolerance in MGH miniature swine: the role of intra-graft and peripheral factors in long-term tolerance.
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DOI：
10.1111/ajt.12816
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Yamada K
中科院分区：
文献类型：
--
作者：
Scalea JR;Okumi M;Villani V;Shimizu A;Nishimura H;Gillon BC;Torabi R;Cormack T;Moran S;LeGuern C;Sachs DH;Yamada K
我们以前已经证明，长期耐受（LTT）的MHC I类不匹配的肾移植物可以实现短期的环孢素。为了研究该模型中耐受性的调控机制，我们评估了移植物内和外周血中因子在维持稳定耐受性中的相对作用。12例MHC I类不匹配的原代肾LTT受体接受了由供体特异性输血（DST），然后进行白细胞分离术组成的治疗，以去除外周血白细胞，包括推定的调节性T细胞（T细胞）。治疗后，临床随访了两只对照动物，10只动物接受了第二个供体MHC匹配的肾脏。对照组动物均未出现排斥反应，而10只再次移植动物中有8只出现排斥反应危机或第二次移植完全排斥反应。体外试验证实，去除的白细胞是抑制性的，血液和肾移植物中的CD4+Foxp3+ Treg重建与经历短暂排斥危机的动物恢复正常肾功能相关。这些数据表明，可接受的肾移植物的成分以及外周调节成分都有助于形成MHC I类错配同种异体移植耐受所需的致耐受性环境。
We have previously demonstrated that long-term tolerance (LTT) of an MHC class-I mismatched renal allograft can be achieved with a short course of cyclosporine. In order to examine regulatory mechanisms underlying tolerance in this model, we assessed the contributions of factors within the graft and in the peripheral blood for their relative roles in the maintenance of stable tolerance. Twelve LTT recipients of MHC class-I mismatched primary kidneys were subjected to a treatment consisting of donor-specific transfusion (DST) followed by leukapheresis, in order to remove peripheral leukocytes, including putative regulatory T cells (Tregs). Following treatment, two controls were followed clinically and 10 animals received a second, donor-MHC-matched kidney. Neither control animal showed evidence of rejection, while 8 of 10 re-transplanted animals developed either rejection crisis or full rejection of the second transplant. In vitro assays confirmed that the removed leukocytes were suppressive and that CD4+Foxp3+ Treg reconstitution in blood and kidney grafts correlated with return to normal renal function in animals experiencing transient rejection crises. These data indicate that components of accepted kidney grafts as well as peripheral regulatory components both contribute to the tolerogenic environment required for tolerance of MHC class-I mismatched allotransplants.
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DOI：
10.1073/pnas.0605159103
发表时间：
2006-12-12
影响因子：
11.1
作者：
Nobori, Shuji;Shimizu, Akira;Yamada, Kazuhiko
通讯作者：
Yamada, Kazuhiko
影响因子：
6.2
作者：
SACHS, DH;LEIGHT, G;ROSENBERG, S
通讯作者：
ROSENBERG, S
影响因子：
6.2
作者：
Blancho, G;Gianello, PR;LeGuern, C
通讯作者：
LeGuern, C
影响因子：
6.2
作者：
Ierino, FL;Yamada, K;Sachs, DH
通讯作者：
Sachs, DH
影响因子：
6.2
作者：
Vagefi, PA;Ierino, FL;Yamada, K
通讯作者：
Yamada, K