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使用 AMD3100 显著动员常规和调节性 T 细胞。

Significant mobilization of both conventional and regulatory T cells with AMD3100.

机构信息

Department of Pediatrics, Children's Healthcare of Atlanta and the Emory Transplant Center, Emory University School of Medicine, 101 Woodruff Circle NE, Atlanta, GA 30322, USA.

出版信息

Blood. 2011 Dec 15;118(25):6580-90. doi: 10.1182/blood-2011-06-359331. Epub 2011 Oct 11.

Abstract

In this study, we used the rhesus macaque model to determine the impact that AMD3100 has on lymphocyte mobilization, both alone and in combination with G-CSF. Our results indicate that, unlike G-CSF, AMD3100 substantially mobilizes both B and T lymphocytes into the peripheral blood. This led to significant increases in the peripheral blood content of both effector and regulatory T-cell populations, which translated into greater accumulation of these cells in the resulting leukapheresis products. Notably, CD4(+)/CD25(high)/CD127(low)/FoxP3(+) Tregs were efficiently mobilized with AMD3100-containing regimens, with as much as a 4.0-fold enrichment in the leukapheresis product compared with G-CSF alone. CD8(+) T cells were mobilized to a greater extent than CD4(+) T cells, with accumulation of 3.7 ± 0.4-fold more total CD8+ T cells and 6.2 ± 0.4-fold more CD8(+) effector memory T cells in the leukapheresis product compared with G-CSF alone. Given that effector memory T-cell subpopulations may mediate less GVHD compared with other effector T-cell populations and that Tregs are protective against GVHD, our results indicate that AMD3100 may mobilize a GVHD-protective T-cell repertoire, which would be of benefit in allogeneic hematopoietic stem cell transplantation.

摘要

在这项研究中,我们使用恒河猴模型来确定 AMD3100 对淋巴细胞动员的影响,包括单独使用和与 G-CSF 联合使用的情况。我们的结果表明,与 G-CSF 不同,AMD3100 大量动员 B 和 T 淋巴细胞进入外周血。这导致效应和调节性 T 细胞群体在外周血中的含量显著增加,进而导致这些细胞在外周血成分单采产物中的积累增加。值得注意的是,与 G-CSF 单独使用相比,AMD3100 联合方案可有效动员 CD4(+)/CD25(high)/CD127(low)/FoxP3(+) Tregs,在外周血成分单采产物中的富集程度高达 4.0 倍。与 CD4(+) T 细胞相比,CD8(+) T 细胞动员程度更高,在外周血成分单采产物中,总 CD8+T 细胞积累增加了 3.7±0.4 倍,CD8(+)效应记忆 T 细胞增加了 6.2±0.4 倍。鉴于效应记忆 T 细胞亚群与其他效应 T 细胞群相比可能介导的移植物抗宿主病较少,而 Tregs 可预防移植物抗宿主病,我们的结果表明,AMD3100 可能动员一种移植物抗宿主病保护的 T 细胞库,这将有益于异基因造血干细胞移植。

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