Journal
BLOOD
Volume 118, Issue 25, Pages 6580-6590Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-06-359331
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Funding
- National Heart, Lung, and Blood Institute
- Yerkes National Primate Research Center [RR00165]
- Burroughs Wellcome Fund (Career Award in the Biomedical Sciences)
- National Institute of Dental and Craniofacial Research [DE018339, DE019397]
- [2U19 AI051731]
- [1 R01 HL095791]
- [2U24 RR018109]
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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)
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