title: Potency of Both Human Th1 and NK Helper Cell Activation is Determined by IL-12p70-Producing PAMP-Matured DCs.
abstract: Besides T helper (Th) cells, natural killer (NK) cells have also been described to participate in the shaping of dendritic cell (DC)-mediated adaptive immune responses. At present, it remains unclear to what extent the induction of these NK helper cell immune mechanisms is coupled with Th responses and whether both helper immune responses are induced by the same DC upon specific pathogen recognition receptor (PRR) stimulation. In this study, we demonstrate that maturation of DCs with a cocktail containing FMKp (membrane fragments of Klebsiella pneumoniae) mounts both Th cell and NK cell helper responses in a PRR-triggered dose-dependent manner as determined by the capacity of the helper cells to produce IFN-γ. Furthermore, by triggering an additional PRR pathway [FMKp in combination with poly(I:C) lyovec], we reveal that both approaches modulate the amount of DC-derived IL-12p70 and that this cytokine is the key determinant of the DC-induced Th1 and NK cell helper responses. Moreover, all PRR triggers able to induce IL-12-producing mature DCs are sufficient to induce these helper responses. We propose the existence of a single program used by DCs to induce potent cellular immune responses by stimulating both T helper and NK cell helper processes. This knowledge can help to select the proper PRR triggers in preventive and therapeutic vaccine design.
authors.affiliation: 1 Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+ , Maastricht, The Netherlands .
authors.forename: Tammy
authors.initials: T
authors.lastname: Oth
authors.affiliation: 1 Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+ , Maastricht, The Netherlands .
authors.forename: Catharina H M J
authors.initials: CH
authors.lastname: Van Elssen
authors.affiliation: 1 Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+ , Maastricht, The Netherlands .
authors.forename: Melanie C A
authors.initials: MC
authors.lastname: Schnijderberg
authors.affiliation: 1 Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+ , Maastricht, The Netherlands .
authors.forename: Birgit L M G
authors.initials: BL
authors.lastname: Senden-Gijsbers
authors.affiliation: 1 Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+ , Maastricht, The Netherlands .
authors.forename: Wilfred T V
authors.initials: WT
authors.lastname: Germeraad
authors.affiliation: 1 Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+ , Maastricht, The Netherlands .
authors.forename: Gerard M J
authors.initials: GM
authors.lastname: Bos
authors.affiliation: 2 Tissue Typing Laboratory, Department of Transplantation Immunology, School of Oncology and Developmental Biology, Maastricht University Medical Center+ , Maastricht, The Netherlands .
authors.forename: Joris
authors.initials: J
authors.lastname: Vanderlocht
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008566:Membranes / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D018664:Interleukin-12; D007371:Interferon-gamma; D011070:Poly I-C