PuSH - Publication Server of Helmholtz Zentrum München: 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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Lichtenegger, F.S.* ; Mueller, K.* ; Otte, B.* ; Beck, B.* ; Hiddemann, W.* ; Schendel, D.J. ; Subklewe, M.*

CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer cell activation by toll-like receptor-induced dendritic cells.

PLoS ONE 7:e44266 (2012)

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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. Methodology/Principal Findings: 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-gamma 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/Significance: 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.

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