1,25-dihydroxyvitamin D-3 inhibits dendritic cell differentiation and maturation in vitro

Objective. Because of its potent immunosuppressive properties in vitro as w ell as in vivo, we studied the effect of 1,25-dihydroxyvitamin D-3 (calcitr iol) on differentiation, maturation, and function of dendritic cells (DC). Materials and Methods. Monocyte-derived DCs were generated with GM-CSF plus IL-4, and maturation was induced by a 2-day exposure to TNF alpha. DCs wer e derived from CD34(+) progenitors using SCF plus GM-CSF plus TNF alpha, Fo r differentiation studies, cells were exposed to calcitriol at concentratio ns of 10(-9)-10(-7) M at days 0, 6, and 8, respectively. The obtained cell populations were evaluated by morphology, phenotype, and function. Results, When added at day 0, calcitriol blocked DC differentiation from mo nocytes and inhibited the generation of CD1a(+) cells from progenitor cells while increasing CD14(+) cells, Exposure of immature DCs to calcitriol at day 6 resulted in a loss of the DC-characteristic surface molecule CD1a, do wnregulation of the costimulatory molecules CD40 and CD80, and MHC class II expression, whereas the monocyte/macrophage marker CD14 was clearly reindu ced, In addition, calcitriol hindered TNF alpha-induced DC maturation, whic h is usually accompanied with induction of CD83 expression and upregulation of costimulatory molecules. In contrast, the mature CD83(+) DCs remained C D1a(+)CD14(-) when exposed to calcitriol, The capacity of cytokine-treated cells to stimulate allogeneic and autologous T cells and to take up soluble antigen was inhibited by calcitriol. Conclusion. The potent suppression of DC differentiation, the reversal of D C phenotype, and function in immature DCs, as well as the inhibition of DC maturation by calcitriol, may explain some of its immunosuppressive propert ies, (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.