Significant mobilization of both conventional and regulatory T cells with AMD3100
Significant mobilization of both conventional and regulatory T cells with AMD3100
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DOI：
10.1182/blood-2011-06-359331
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发表时间：
2011-12-15
期刊：
影响因子：
20.3
通讯作者：
Donahue, Robert E.
中科院分区：
文献类型：
--
作者：
Kean, Leslie S.;Sen, Sharon;Donahue, Robert E.
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，无论是单独使用还是与G-CSF联合使用。我们的研究结果表明，与G-CSF不同，AMD3100可以将B淋巴细胞和T淋巴细胞动员到外周血中。这导致外周血中效应t细胞群和调节性t细胞群的含量显著增加，这转化为这些细胞在产生的白细胞分离产物中的更大积累。值得注意的是，CD4(+)/CD25（高）/CD127（低）/FoxP3(+) Tregs在含有amd3100的方案中被有效调动，与单独使用G-CSF相比，白细胞分离产物中的富集程度高达4.0倍。CD8(+) T细胞的动员程度大于CD4(+) T细胞，与单独使用G-CSF相比，白细胞分离产物中CD8(+) T细胞总量多3.7 +/- 0.4倍，CD8（+）效应记忆T细胞总量多6.2 +/- 0.4倍。考虑到效应记忆t细胞亚群介导的GVHD比其他效应t细胞亚群少，而且Tregs对GVHD具有保护作用，我们的研究结果表明AMD3100可能调动GVHD保护t细胞库，这将有利于异体造血干细胞移植。(血。2011;118 (25):6580 - 6590)
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 sub-populations 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. (Blood. 2011;118(25):6580-6590)