A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 ligand and interferon-gamma treatment

Blood. 2000 Nov 15;96(10):3499-504.


Dendritic cells (DCs) may arise from multiple lineages and progress through a series of intermediate stages until fully mature, at which time they are capable of optimal antigen presentation and T-cell activation. High cell surface expression of CD83 is presumed to correlate with full maturation of DCs, and a number of agents have been shown to increase CD83 expression on DCs. We hypothesized that interleukin 12 (IL-12) expression would be a more accurate marker of functionally mature DCs capable of activating antigen-specific T cells. We used combinations of signaling through CD40, using CD40 ligand trimer (CD40L), and interferon gamma to demonstrate that CD83 expression is necessary but not sufficient for optimal production of IL-12 by DCs. Phenotypically mature DCs could be induced to produce high levels of IL-12 p70 only when provided 2 simultaneous stimulatory signals. By intracellular cytokine detection, we determined that only a subset of cells that express high levels of CD80 and CD83 generate large amounts of IL-12. DCs matured with both signals are superior to DCs stimulated with the individual agents in activating antigen-specific T cell in vitro. These findings have important implications regarding the identification, characterization, and clinical application of functionally mature DCs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Antigen Presentation / drug effects
  • Antigens, CD
  • B7-1 Antigen / metabolism
  • B7-1 Antigen / physiology
  • Biomarkers
  • CD40 Ligand / pharmacology*
  • CD83 Antigen
  • Cell Culture Techniques
  • Cell Differentiation
  • Cytotoxicity Tests, Immunologic
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Fluorescent Antibody Technique, Direct
  • Humans
  • Immunoglobulins / metabolism
  • Immunoglobulins / physiology
  • Immunophenotyping
  • Interferon-gamma / pharmacology*
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology
  • Monocytes / cytology
  • Protein Subunits


  • Adjuvants, Immunologic
  • Antigens, CD
  • B7-1 Antigen
  • Biomarkers
  • Immunoglobulins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Protein Subunits
  • CD40 Ligand
  • Interleukin-12
  • Interferon-gamma