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PLoS One. 2012;7(9):e44266. doi: 10.1371/journal.pone.0044266. Epub 2012 Sep 4.

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

Author information

1
Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany. Felix.Lichtenegger@med.uni-muenchen.de

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.

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-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/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.

PMID:
22962607
PMCID:
PMC3433478
DOI:
10.1371/journal.pone.0044266
[Indexed for MEDLINE]
Free PMC Article

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