The imidazoquinolines, imiquimod and R-848, induce functional, but not phenotypic, maturation of human epidermal Langerhans' cells

Clin Immunol. 2000 Jan;94(1):13-23. doi: 10.1006/clim.1999.4804.

Abstract

Imiquimod (R-837) and its more potent derivative (R-848) are imidazoquinolines that have adjuvant activity in cultured human mononuclear cells. Its mechanism of action on epidermal antigen-presenting cells is not known. The purpose of the present investigation was to determine whether imiquimod and R-848 affect human epidermal Langerhans' cells' (LC) in vitro maturation. Pulse incubations (6-16 h) of cultured unfractionated epidermal cells or highly enriched LC suspensions with either imiquimod or R-848 (0. 05-5.0 microg/ml of culture medium) reproducibly enhanced their ability to induce T-cell proliferation in a primary mixed lymphocyte reaction. There was a 30 to 300% increase in T-lymphocyte proliferation induced by either imiquimod- or R-848-treated LC when compared to control, untreated LC. IFN-gamma secretion by T-lymphocytes stimulated by imiquimod- or R-848-treated LC was increased compared to control, untreated LC. After a 6-h incubation, phenotypic analysis of control-, imiquimod-, or R-848-treated LC indicated that such antigen-presenting cells were in an "intermediate" state of maturation (CD1a(+), HLA-DR, DP, DQ(bright+), CD40(low+), CD86(high+), and CD80(low+)). RNase protection assays demonstrated that either imiquimod or R-848 treatments increased steady-state transcripts encoding for IL-12 p40, IL-1beta, TNF-alpha, and IL-1 receptor antagonist by LC. These data indicate that imiquimod and R-848 dissociate the functional maturation (cytokine-mediated) and phenotypic maturation of epidermal LC. These data warrant further exploration for the use of imidazoquinoline-treated LC or other DC subsets for processing and presentation of viral peptides to Th-lymphocytes as a novel vaccine strategy to induce protective antiviral responses.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Aminoquinolines / pharmacology*
  • Antigen Presentation / drug effects
  • Cell Division / drug effects
  • Cell Division / genetics
  • Cells, Cultured
  • Cytokines / genetics
  • Gene Expression / drug effects
  • Humans
  • Imidazoles / pharmacology*
  • Imiquimod
  • Immunologic Factors / pharmacology*
  • Langerhans Cells / cytology*
  • Lymphocyte Culture Test, Mixed
  • Phenotype
  • Th1 Cells / cytology

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Cytokines
  • Imidazoles
  • Immunologic Factors
  • Imiquimod
  • resiquimod