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Significant mobilization of both conventional and regulatory T cells with AMD3100

Authors :
Daniel E. L. Promislow
Olusegun O. Onabajo
Sharon Sen
Robert E. Donahue
Linda Stempora
Jennifer Robertson
Joseph J. Mattapallil
Karnail Singh
Mark E. Metzger
Aylin C. Bonifacino
Leslie S. Kean
Source :
Blood. 118:6580-6590
Publication Year :
2011
Publisher :
American Society of Hematology, 2011.

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+/CD25high/CD127low/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.

Details

ISSN :
15280020 and 00064971
Volume :
118
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi.dedup.....02cce8b596edf537f09936893be4fef8
Full Text :
https://doi.org/10.1182/blood-2011-06-359331