Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development

Eur J Immunol. 2009 Oct;39(10):2865-76. doi: 10.1002/eji.200939486.


Myeloid-derived suppressor cells (MDSC) and DC are major controllers of immune responses against tumors or infections. However, it remains unclear how DC development and MDSC suppressor activity both generated from myeloid precursor cells are regulated. Here, we show that the combined treatment of BM-derived MDSC with LPS plus IFN-gamma inhibited the DC development but enhanced MDSC functions, such as NO release and T-cell suppression. This was not observed by the single treatments in vitro. In the spleens of healthy mice, we identified two Gr-1(low)CD11b(high)Ly-6C(high)SSC(low)Mo-MDSC and Gr-1(high)CD11b(low)PMN-MDSC populations with suppressive potential, whereas Gr-1(high)CD11b(high) neutrophils and Gr-1(low)CD11b(high)SSC(low) eosinophils were not suppressive. Injections of LPS plus IFN-gamma expanded these populations within the spleen but not LN leading to the block of the proliferation of CD8(+) T cells. At the same time, their capacity to develop into DC was impaired. Together, our data suggest that spleens of healthy mice contain two subsets of MDSC with suppressive potential. A two-signal-program through combined LPS and IFN-gamma treatment expands and fully activates MDSC in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • CD11b Antigen / metabolism
  • Cell Differentiation / drug effects*
  • Cell Differentiation / immunology
  • Cytokines / pharmacology
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology*
  • Interferon-gamma / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Lymph Nodes / cytology
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Cells / cytology
  • Myeloid Cells / drug effects*
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Nitric Oxide / metabolism
  • Ovalbumin / immunology
  • Receptors, Chemokine / metabolism
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation


  • CD11b Antigen
  • Cytokines
  • Gr-1 protein, mouse
  • Lipopolysaccharides
  • Receptors, Chemokine
  • Nitric Oxide
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ovalbumin