Dendritic cell maturation and subsequent enhanced T-cell stimulation induced with the novel synthetic immune response modifier R-848

Cell Immunol. 1999 Oct 10;197(1):62-72. doi: 10.1006/cimm.1999.1555.


Agents that enhance dendritic cell maturation can enhance T-cell activation and therefore may improve the efficiency of vaccines or improve cellular immunotherapy. Previously, we demonstrated that a novel low-molecular-weight synthetic immune response modifier, R-848, induces IL-12 and IFN-alpha secretion from monocytes and macrophages. Here we report that R-848 induces the maturation of human monocyte-derived dendritic cells. Characteristic of dendritic cell maturation, R-848 treatment induces cell surface expression of CD83 and increases cell surface expression of CD80, CD86, CD40, and HLA-DR. Additionally, R-848 induces cytokine (IL-6, IL-12, TNF-alpha, IFN-alpha) and chemokine (IL-8, MIP-1alpha, MCP-1) secretion from dendritic cells. Most significantly, R-848 enhances dendritic cell antigen presenting function, as measured by increased T-cell proliferation and T-cell cytokine secretion in both allogeneic and autologous T-cell systems. Consequently, low-molecular-weight synthetic molecules such as R-848 and its derivatives may be useful as vaccine adjuvants or as ex vivo stimulators of dendritic cells for cellular immunotherapy.

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, Surface / biosynthesis
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Division / drug effects
  • Cells, Cultured
  • Chemokines / biosynthesis
  • Chemokines / metabolism
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • Imidazoles / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Monocytes / cytology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / metabolism


  • Antigens, CD
  • Antigens, Surface
  • Chemokines
  • Cytokines
  • Imidazoles
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • resiquimod