TY - JOUR
T1 - Significant mobilization of both conventional and regulatory T cells with AMD3100
AU - Kean, Leslie S.
AU - Sen, Sharon
AU - Onabajo, Olusegun
AU - Singh, Karnail
AU - Robertson, Jennifer
AU - Stempora, Linda
AU - Bonifacino, Aylin C.
AU - Metzger, Mark E.
AU - Promislow, Daniel E.L.
AU - Mattapallil, Joseph J.
AU - Donahue, Robert E.
PY - 2011/12/15
Y1 - 2011/12/15
N2 - 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/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 extentthan 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.
AB - 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/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 extentthan 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.
UR - http://www.scopus.com/inward/record.url?scp=84055218925&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-06-359331
DO - 10.1182/blood-2011-06-359331
M3 - Article
C2 - 21989987
AN - SCOPUS:84055218925
SN - 0006-4971
VL - 118
SP - 6580
EP - 6590
JO - Blood
JF - Blood
IS - 25
ER -