CD86 and IL-12p70 Are Key Players for T Helper 1 Polarization and Natural Killer Cell Activation by Toll-Like Receptor-Induced Dendritic Cells |
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Authors: | Felix S Lichtenegger Katharina Mueller Bettina Otte Barbara Beck Wolfgang Hiddemann Dolores J Schendel Marion Subklewe |
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Institution: | 1. Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany.; 2. Institute of Molecular Immunology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.; University of Bergen, Norway, |
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Abstract: | BackgroundDendritic 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.Methodology/Principal FindingsWe 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/SignificanceTLR-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. |
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