Phenotypic and functional outcome of human monocytes or monocyte-derived dendritic cells in a dermal equivalent

The dermis harbors a true dendritic cell population that could elicit prima ry allogeneic T cell responses in vitro and contact hypersensitivity reacti ons in vivo. The origin of dermal dendritic cells remains poorly understood , however. In this study, we analyzed the fate of monocytes or monocyte-der ived dendritic cells in a dermal equivalent. Freshly isolated monocytes or monocytes cultured for 6 d with either GM-CSF/IL-4 or GM-CSF/IL-4/TGF-beta1 (TGF-DC) were seeded in a collagen solution with normal human fibroblasts. The lattices were cultured for 7-14 d in the presence, or absence, of the exogenous cytokines, before phenotypic and functional studies were performe d. Supply of exogenous cytokines allows the appearance of typical CD1a(+)/C D14(-)/CD68(low) dendritic cells with significant allostimulatory property, regardless of the cell type incorporated into the lattices. In cytokine-fr ee conditions, monocytes and GM-CSF/IL-4-derived dendritic cells give rise to a CD1a(-)/CD14(+)/CD68(high) monocyte/macrophage population with no allo stimulatory property. When incorporated into the lattices in the absence of exogenous cytokines the TGF-DC express few CD68 and FXIIIa, Interestingly, these cells do not all convert into the CD14(+)/CD1a(-) population. Indeed , a small HLA-DR+/CD1a(+)/CD14(-) subset was consistently found, which repr esents about one-third of the HLA-DR+ cells. Moreover, TGF-DC recovered fro m the lattices after culture without cytokines do display a significant all ostimulatory function. Thus, in the absence of exogenous cytokines, only La ngerhans-cell-like dendritic cells can retain the typical dendritic cell fe atures when inserted in a dermal environment. Taken together, these results may provide evidence supporting an epidermal origin of dermal dendritic ce lls.