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首页> 外文期刊>Transplantation: Official Journal of the Transplantation Society >Donor bone marrow-derived chimeric cells present in renal transplant recipients infused with donor marrow. I. Potent regulators of recipient antidonor immune responses.
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Donor bone marrow-derived chimeric cells present in renal transplant recipients infused with donor marrow. I. Potent regulators of recipient antidonor immune responses.

机译：存在于供体骨髓中的供肾移植受体中存在的供体骨髓来源的嵌合细胞。 I.受体抗供体免疫反应的有效调节剂。

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BACKGROUND: Even though a number of transplant centers have adopted donor-specific bone marrow cell (DBMC) infusions to enhance donor cell chimerism, to date there has been no direct evidence linking chimerism with tolerance induction in human organ transplant recipients. METHODS: Cells of donor phenotype were isolated 1 year postoperatively from the peripheral blood lymphocytes and iliac crest bone marrow of 11 living-related-donor (LRD) renal transplant recipients, who had received perioperative donor bone marrow cell infusions. These recipient-derived donor (RdD) cells were characterized phenotypically by flow cytometric analysis and functionally as modulators in mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. RESULTS: The yield of RdD cells ranged from 0.1 to O.9% of the starting material with the majority being TcRalphabeta, CD3 positive T cells, a substantial percentage of which coexpressed CD28. At 1 year posttransplant almost 50% of the LRD-kidney/DBMC recipients tested so far exhibited donor-specific unresponsiveness in MLR (7/17) and CML (6/13) reactions and this trend was further enhanced at 23 years. In the recipients with residual positive antidonor immune responses, the RdD cells inhibited recipient antidonor MLR and CML responses significantly more strongly than freshly isolated and similarly treated iliac crest bone marrow cells from the donor. RdD cells also inhibited the MLR of the recipient to third party allogeneic stimulator cells; however, this nonspecific effect was significantly weaker than specific inhibition. We also established long-term bone marrow cultures stimulated every 2 weeks with irradiated alogeneic feeder cells, that had similar functional properties thus possibly providing us with an in vitro correlate the RdD cells. CONCLUSIONS: These results clearly support the notion that the infused donor cells play a positive role in the induction and/or maintenance of transplant tolerance.
机译：背景：尽管许多移植中心已经采用输注特定供体的骨髓细胞（DBMC）来增强供体细胞嵌合体，但迄今为止，尚无直接证据将嵌合体与人体器官移植接受者的耐受诱导联系起来。方法：术后1年，从11名接受围手术期供体骨髓细胞输注的活体供体（LRD）肾移植受者的外周血淋巴细胞和骨骨髓中分离出供体表型细胞。这些受体来源的供体（RdD）细胞通过流式细胞仪分析进行表型表征，并在混合淋巴细胞反应（MLR）和细胞介导的淋巴溶解（CML）分析中作为调节剂发挥功能。结果：RdD细胞的产量占起始原料的0.1％至0.9％，大部分为TcRalphabeta，CD3阳性T细胞，其中很大一部分共表达CD28。移植后第1年，到目前为止，接受测试的近50％的LRD-肾脏/ DBMC接受者在MLR（7/17）和CML（6/13）反应中表现出供体特异性无反应，并且这种趋势在23岁时进一步增强。在具有残留的阳性抗供体免疫反应的受体中，RdD细胞比来自供体的新鲜分离和相似处理的骨骨髓细胞抑制作用强得多。 RdD细胞还抑制了受体对第三方同种异体刺激细胞的MLR;然而，这种非特异性作用明显弱于特异性抑制作用。我们还建立了每两周用辐照的自养饲养细胞刺激的长期骨髓培养物，它们具有相似的功能特性，因此可能为我们提供了与RdD细胞的体外相关性。结论：这些结果清楚地支持了注入的供体细胞在诱导和/或维持移植耐受性中发挥积极作用的观点。

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