Significant mobilization of both conventional and regulatory T cells with AMD3100

Blood. 2011 Dec 15;118(25):6580-90. doi: 10.1182/blood-2011-06-359331. Epub 2011 Oct 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism
  • Drug Synergism
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization / methods*
  • Heterocyclic Compounds / pharmacology*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Leukapheresis / methods
  • Lymphocyte Count
  • Macaca mulatta
  • Receptors, CXCR4 / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Forkhead Transcription Factors
  • Heterocyclic Compounds
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Receptors, CXCR4
  • Granulocyte Colony-Stimulating Factor
  • plerixafor octahydrochloride