title: CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer cell activation by Toll-like receptor-induced dendritic cells.
abstract: BACKGROUND
  Dendritic cells (DCs) determine the activation and polarization of T cells via expression of costimulatory molecules and secretion of cytokines. The function of DCs derived from monocytes ex vivo strongly depends on the composition of the maturation cocktail used.
  
  
  RESULTS
  We analyzed the effect of costimulatory molecule expression and cytokine secretion by DCs on T and natural killer (NK) cell activation by conducting a head-to-head comparison of a Toll-like receptor (TLR) agonist-based cocktail with the standard combination of proinflammatory cytokines or IL-10 alone. We could show that TLR-induced DCs are characterized by a predominance of costimulatory over coinhibitory molecules and by high secretion of IL-12p70, but not IL-10. Functionally, these signals translated into an increase in IFN-γ secreting Th1 cells and a decrease in regulatory T cells. T cell activation and polarization were dependent on IL-12p70 and CD86, but remarkably not on CD80 signaling. By means of IL-12p70 secretion, only TLR-induced DCs activated NK cells.
  
  
  CONCLUSIONS
  TLR-matured DCs are highly suitable for application in immunotherapeutic strategies that rely on strong type 1 polarization and NK cell activation. Their effects particularly depend on high CD86 expression and IL-12p70 secretion.
authors.affiliation: Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. Felix.Lichtenegger@med.uni-muenchen.de
authors.forename: Felix S
authors.initials: FS
authors.lastname: Lichtenegger
authors.forename: Katharina
authors.initials: K
authors.lastname: Mueller
authors.forename: Bettina
authors.initials: B
authors.lastname: Otte
authors.forename: Barbara
authors.initials: B
authors.lastname: Beck
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Dolores J
authors.initials: DJ
authors.lastname: Schendel
authors.forename: Marion
authors.initials: M
authors.lastname: Subklewe
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma