G-CSF stem cell mobilization in human donors induces polymorphonuclear and mononuclear myeloid-derived suppressor cells

Clin Immunol. 2012 Apr;143(1):83-7. doi: 10.1016/j.clim.2012.01.011. Epub 2012 Jan 30.

Abstract

The role of myeloid-derived suppressor cells (MDSC) is emerging in transplantation. An expansion of myeloid progenitor cells with suppressive capacity has been reported to occur as a bystander phenomenon in the course of allogeneic hematopoietic stem cell transplantation (allo-HSCT) protocols, particularly, in mice during bone marrow chimerism induction and in human stem cell donors during G-CSF-mobilization protocols. Hypothesizing that such 'regulatory myeloid cells' play a role in regulating post-transplant T-cell alloreactivity, we performed a phenotypical and functional characterization of these cells in peripheral blood stem cell grafts of G-CSF-treated donors. We demonstrate that expanding myeloid cells in the peripheral blood of G-CSF-mobilized donors comprise the typical phenotype of the mononuclear and polymorphonuclear MDSC-subtypes that were recently described in cancer patients, and that both MDSC-subsets have the capacity to regulate alloreactive T-cell responses in-vitro. This study provides the basis for investigating the clinical relevance of MDSC and MDSC-subtypes in human allo-HSCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Donors*
  • CD11b Antigen / immunology
  • CD11b Antigen / metabolism
  • Cell Proliferation / drug effects
  • Flow Cytometry
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Immunosuppression
  • Leukocyte Common Antigens / immunology
  • Leukocyte Common Antigens / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lewis X Antigen / immunology
  • Lewis X Antigen / metabolism
  • Myeloid Cells / drug effects*
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Peripheral Blood Stem Cell Transplantation / methods*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transplantation, Homologous

Substances

  • CD11b Antigen
  • Lewis X Antigen
  • Granulocyte Colony-Stimulating Factor
  • Leukocyte Common Antigens