G-CSF mobilizes slanDCs (6-sulfo LacNAc+ dendritic cells) with a high proinflammatory capacity

Blood. 2007 Oct 15;110(8):3078-81. doi: 10.1182/blood-2006-12-062984. Epub 2007 Jul 6.

Abstract

Donor dendritic cells (DCs) play a pivotal role in the induction of immunity and tolerance after peripheral blood stem cell transplantation (PBSCT). Treatment of healthy donors with granulocyte-colony stimulating factor (G-CSF) increases the numbers of tolerogenic DCs and T cells among mobilized blood leukocytes in the graft. SlanDCs (6-sulfo LacNAc+ DCs), a major source of IL-12 and TNF-alpha in blood, have not been studied in this respect. Here, we demonstrate that slanDCs (14.9 x 10(6)/L to 64.0 x 10(6)/L) are efficiently mobilized by G-CSF and retain their capacity to produce IL-12 and TNF-alpha at high levels. Furthermore, G-CSF-mobilized slanDCs programmed the differentiation of Th1 cells and displayed a particularly strong capacity to stimulate the proliferation of naive allogeneic T cells. Thus, slanDCs transfused into recipients of allogeneic peripheral blood stem cell (PBSC) transplants are functionally fully capable and may be critical in supporting graft-versus-host disease as well as graft-versus-leukemia effects.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Amino Sugars
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Graft vs Host Disease / immunology
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Inflammation / immunology*
  • Interleukin-12 / biosynthesis
  • Lipopolysaccharides / metabolism*
  • Transplantation Immunology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • 6-sulfo-LacNac
  • Adjuvants, Immunologic
  • Amino Sugars
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor
  • Interleukin-12