Induction of Treg by monocyte-derived DC modulated by vitamin D3 or dexamethasone: differential role for PD-L1

Eur J Immunol. 2009 Nov;39(11):3147-59. doi: 10.1002/eji.200839103.


Specific therapy with modulated DC may restore immunological tolerance, thereby obviating the need for chronic immunosuppression in transplantation or autoimmunity. In this study we compared the tolerizing capacity of dexamethasone (Dex)- and 1 alpha,25-dihydroxyvitamin D3 (VD3)-modulated DC. Treatment of monocytes with either VD3 or Dex resulted in DC with stable, semi-mature phenotypes compared with standard DC, with intermediate levels of co-stimulatory and MHC class II molecules, which remained unaltered after subsequent pro-inflammatory stimulation. IL-12p70 secretion was lost by VD3- and Dex-DC, whereas IL-10 secretion was unaffected. VD3-DC distinctly produced large amounts of TNF-alpha. Both VD3- and Dex-DC possessed the capacity to convert CD4 T cells into IL-10-secreting Treg potently suppressing the proliferation of responder T cells. However, only Treg induced by VD3-DC exhibited antigen specificity. VD3-, but not Dex-, DC expressed significant high levels of PD-L1 (programmed death-1 ligand), upon activation. Blockade of PD-L1 during priming redirected T cells to produce IFN-gamma instead of IL-10 and abolished acquisition of regulatory capacity. Our findings demonstrate that both VD3- and Dex-DC possess durable but differential tolerogenic features, acting via different mechanisms. Both are potentially useful to specifically down-regulate unwanted immune responses and induce immune tolerance. These modulated DC appear suitable as adjuvant in antigen-specific clinical vaccination intervention strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • B7-1 Antigen / immunology*
  • B7-H1 Antigen
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Separation
  • Chemotaxis, Leukocyte / immunology
  • Cholecalciferol / pharmacology*
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dexamethasone / pharmacology*
  • Flow Cytometry
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology
  • Immunomodulation / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / immunology*
  • Monocytes / drug effects
  • Monocytes / immunology
  • Peptides / immunology*
  • Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology*


  • Anti-Inflammatory Agents
  • B7-1 Antigen
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Cytokines
  • Membrane Glycoproteins
  • Peptides
  • Cholecalciferol
  • Dexamethasone