Differential effects of allergens and irritants on early differentiating monocyte-derived dendritic cells.

Phenotypic modifications induced by contact allergens on monocyte-derived dendritic cells (MoDC) have been proposed as an in vitro alternative method to discriminate potential sensitizers from irritants. However, the sensitivity of the assay remains controversial. In all the studies reported so far, DC treatment with chemicals was carried out after 5 to 6 days of monocyte culture. Here, we first determined the dynamic range of expression of differentiation and activation markers on human MoDC cultured in the presence, or absence, of TGFbeta. At day three of culture, most monocytes have already differentiated into CD1a+/CD14- DC and, in the presence of TGFbeta, they expressed CD40, CD54 or CD86 antigens with lower fluorescence intensity than 5 day-cultured MoDC. Treatment of 3-day cultured TGFbeta-MoDC with all the tested strong and moderate sensitizers, i.e. NiSO(4), DNCB, balm of Peru, isothiazolinone and cinnamic aldehyde, at non-toxic concentrations, induced significant phenotypic changes, whereas the irritant SLS had no effect. However, a large variability was observed in the number and nature of the modified antigens, according to the chemical and the experiments. This implies that many surface antigens must be analyzed and many experiments carried out to use this assay as an alternative screening method for contact sensitizers.