Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration.

Boullart AC, Aarntzen EH, Verdijk P, Jacobs JF, Schuurhuis DH, Benitez-Ribas D, Schreibelt G, van de Rakt MW, Scharenborg NM, de Boer A, Kramer M, Figdor CG, Punt CJ, Adema GJ, de Vries IJ.
Cancer Immunol Immunother. 2008 Nov;57(11):1589-97. Epub 2008 Mar 6.

Dendritic cells (DC) are professional antigen-presenting cells of the immune system that play a key role in regulating T cell-based immunity. In vivo, the capacity of DC to activate T cells depends on their ability to migrate to the T cell areas of lymph nodes as well as on their maturation state. Depending on their cytokine-secreting profile, DC are able to skew the immune response in a specific direction. In particular, IL-12p70 producing DC drive T cells towards a T helper 1 type response. A serious disadvantage of current clinical grade ex vivo generated monocyte-derived DC is the poor IL-12p70 production. We have investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex vivo generated human monocyte-derived DC. We demonstrate that in contrast to cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8 ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced migratory capacity. The addition of prostaglandin E2 (PGE2) improved the migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70 production upon T cell encounter. We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter.

URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2522299/?tool=pubmed

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/18322684

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