G. Guironnet et al., Phenotypic and functional outcome of human monocytes or monocyte-derived dendritic cells in a dermal equivalent, J INVES DER, 116(6), 2001, pp. 933-939
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.