title: Significant mobilization of both conventional and regulatory T cells with AMD3100.
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(+)/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.
authors: 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. Leslie.kean@oz.ped.emory.edu
authors: Leslie S
authors: LS
authors: Kean
authors: Sharon
authors: S
authors: Sen
authors: Olusegun
authors: O
authors: Onabajo
authors: Karnail
authors: K
authors: Singh
authors: Jennifer
authors: J
authors: Robertson
authors: Linda
authors: L
authors: Stempora
authors: Aylin C
authors: AC
authors: Bonifacino
authors: Mark E
authors: ME
authors: Metzger
authors: Daniel E L
authors: DE
authors: Promislow
authors: Joseph J
authors: JJ
authors: Mattapallil
authors: Robert E
authors: RE
authors: Donahue
mesh_terms: D000818:Animals; D001596:Benzylamines; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000080027:Cyclams; D004357:Drug Synergism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007937:Leukapheresis / Q000379:methods; D018655:Lymphocyte Count; D008253:Macaca mulatta; D019718:Receptors, CXCR4 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D051858:Forkhead Transcription Factors; D006571:Heterocyclic Compounds; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor