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