Modulation of phenotype, cytokine production and stimulatory function of CD34+-derived DC by NiCl2 and SDS

One of the most promising alternatives to identify the sensitizing potency of new products is the in vitro culture of human dendritic cells (DC). In v ivo, dendritic cells present in the skin are highly specialized antigen-pre senting cells (APC) of the immune system, which play a crucial role in the induction of allergic reactions. The DC produce specific cytokines and upre gulate specific co-stimulatory molecules in addition to the antigen-MHC com plex in order to promote an optimal T-cell activation. The aim of our study is to assess the phenotype, cytokine production and autologous T-cell stim ulatory capacity of the in vitro CD34+-derived dendritic cells after 24 hou rs of incubation with the metal allergen NiCl2 (100-300 muM) and the irrita nt sodium dodecyl sulfate (SDS; 0.01%), in order to find a sensitive endpoi nt to discriminate between sensitizers and irritants. After exposure to Ni, a significant increase in the number of CD83+ and CD86+ cells was noticed. The intensity of CD86 as well as the intensity of the HLA-DR molecule on t he DC also showed a significant increase. The expression of the co-stimulat ory molecule CD80 was not changed after exposure. SIDS was not able to incr ease the expression of any of the analysed markers. The production of IL-6 increased significantly after exposure of dendritic cells to Ni, but not af ter SIDS exposure. Results on tumor necrosis factor-alpha (TNF-alpha) produ ction are somewhat equivocal. Although not statistically significant, TNF-a lpha was upregulated in one out of three experiments after 48 hours of expo sure to the Ni allergen, but increases were also noticed after exposure to SDS (two out of three experiments). Both exposure to Ni and SIDS caused an upregulation (not significant) in the IL-12 production by DC, but the produ ction was higher in Ni-exposed DC compared to SDS-exposed cells. In none of the exposed DC cultures was it possible to detect IL-1 beta. The antigen-p resenting capacity of the DC in autologous MLR could not be demonstrated. N evertheless, T-cell proliferation after DC stimulation was noticed in allog enic MLR. (C) 2001 Elsevier Science Ltd. All rights reserved.