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添加到骨髓中的粒细胞集落刺激因子动员的外周血单个核细胞有助于在非清髓犬受体中植入:需要CD3细胞。

G-CSF-mobilized peripheral blood mononuclear cells added to marrow facilitates engraftment in nonmyeloablated canine recipients: CD3 cells are required.

作者信息

Zaucha J M, Zellmer E, Georges G, Little M T, Storb R, Storer B, Torok-Storb B

机构信息

Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109-1024, USA.

出版信息

Biol Blood Marrow Transplant. 2001;7(11):613-9. doi: 10.1053/bbmt.2001.v7.pm11760149.

Abstract

Stable mixed donor/host hematopoietic chimerism can be uniformly established in dogs conditioned with 200 cGy TBI before dog leukocyte antigen (DLA)-identical marrow transplantation and immunosuppressed with a short course of mycophenolate mofetil (MMF) and cyclosporine (CSP) after the transplantation. A further decrease in the TBI dose to 100 cGy or the elimination of MMF in this model results in graft rejection. Here we asked whetherthe addition of G-CSF-mobilized peripheral blood mononuclear cells (G-PBMC) to marrow grafts would enhance donor engraftment in dogs conditioned with 100 cGy TBI and given postgrafting immunosuppression with CSP alone. Using this model, 7 of 9 dogs given only marrow cells rejected their grafts within 8 to 17 weeks after transplantation. In contrast, the addition of unmodified G-PBMC to marrow grafts resulted in stable mixed donor/host chimerism in 5 of 8 dogs studied (P = .06). However, addition of the CD3-depleted fraction of G-PBMC, which contained both CD34 cells and CD14 cells, resulted in engraftment in only 1 of 7 recipients. We conclude that adding G-PBMC to marrow grafts replaced the requirement of MMF and 100 cGy of TBI, and that CD3 cells were required to facilitate engraftment of marrow cells in DLA-identical recipients, whereas the additional CD34 cells present in G-PBMC were not sufficient for this effect.

摘要

在进行犬白细胞抗原(DLA)匹配的骨髓移植前,用200 cGy的全身照射(TBI)对犬进行预处理,移植后用短疗程的霉酚酸酯(MMF)和环孢素(CSP)进行免疫抑制,可在犬体内均匀建立稳定的混合供体/宿主造血嵌合体。在此模型中,将TBI剂量进一步降低至100 cGy或去除MMF会导致移植物排斥。在这里,我们探讨了在骨髓移植物中添加粒细胞集落刺激因子(G-CSF)动员的外周血单个核细胞(G-PBMC)是否会增强经100 cGy TBI预处理且移植后仅用CSP进行免疫抑制的犬的供体植入。使用该模型,仅接受骨髓细胞的9只犬中有7只在移植后8至17周内排斥了移植物。相比之下,在骨髓移植物中添加未修饰的G-PBMC,在研究的8只犬中有5只产生了稳定的混合供体/宿主嵌合体(P = 0.06)。然而,添加去除CD3的G-PBMC组分(其中包含CD34细胞和CD14细胞),仅7只受体中的1只实现了植入。我们得出结论,在骨髓移植物中添加G-PBMC可替代MMF和100 cGy TBI的需求,并且需要CD3细胞来促进骨髓细胞在DLA匹配受体中的植入,而G-PBMC中额外存在的CD34细胞不足以产生这种效果。

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