Maturation of human iDCs by IL-18 plus PGE2, but not by each stimulus alone, induced migration toward CCL21 and the secretion of IL-12 and IFN-gamma

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells that initiate the primary immune response and whose functional properties in vivo depend on the maturation stimulus. We describe the functional properties of human monocyte-derived DCs after the maturation of immature DCs (iDCs) for 2 days with LPS (100 ng/ml), PGE2 (1 mu g/ml), CD40L (1 mu g/ml) or IL-18 (200 ng/ml) and with CD40L + PGE2 and IL-18 + PGE2 mixtures at the same concentrations as above. Neither IL-18 nor PGE2 alone stimulated IL-12 or IFN-gamma secretion. When administered simultaneously to 1 x 10(6) iDCs/ml, IL-18 + PGE2 induced the secretion of 131.4 +/- 6.7 pg IL-12/ml and 355 +/- 87 pg IFN-gamma/ml but there was no detectable IL-10 secretion. However, PGE2 alone stimulated the secretion of 208 +/- 89 pg IL-10/ml whereas IL-18 alone did not stimulate the secretion of IL-10, IL-12, TNF-alpha or INF-gamma. When the mixture of CD40L + PGE2 was used, only migration toward CCL19 and CCL21 was induced. CD40L did not stimulate the secretion of IL-10, IL-12, TNF-alpha or IFN-gamma and did not stimulate migration toward CCL19 or CCL21. The extent of stimulation of T cell proliferation was essentially the same for all stimuli at the concentrations given above. New properties such as IL-12 and INF-gamma secretion and migration toward CCL21 emerged when a mixture of IL-18 + PGE2 was employed. These data show that when the pairs of stimuli reported here were used simultaneously their effect was not additive. This system can be used to prepare mDCs with properties useful for cell therapy and also as a model to investigate the mechanisms of cytokine secretion and cell migration.