B. Pulendran et al., Flt3-ligand and granulocyte colony-stimulating factor mobilize distinct human dendritic cell subsets in vivo, J IMMUNOL, 165(1), 2000, pp. 566-572
Dendritic tells (DCs) have a unique ability to stimulate naive T cells. Rec
ent evidence suggests that distinct DC subsets direct different classes of
immune responses in vitro and in vivo, In humans, the monocyte-derived CD11
c(+) DCs induce T cells to produce Th1 cytokines in vitro, whereas the CD11
c(-) plasmacytoid T cell-derived DCs elicit the production of Th2 cytokines
. In this paper we report that administration of either Flt3-1igand (FL) or
G-CSF to healthy human volunteers dramatically increases distinct DC subse
ts, or DC precursors, in the blood. FL increases both the CD11c(+) DC subse
t (48-fold) and the CD11c(-) IL-3R(+) DC precursors (13-fold). In contrast,
G-CSF only increases the CD11c(-) precursors (>7-fold). Freshly sorted CD1
1c(+) but not CD11c(-) cells stimulate CD4(+) T cells in an allogeneic MLR,
whereas only the CD11c(-) cells can be induced to secrete high levels of I
FN-alpha, in response to influenza virus. CD11c(+) and CD11c(-) cells can m
ature in vitro with GM-CSF + TNF-alpha or with IL-3 + CD40 ligand, respecti
vely. These two subsets up-regulate MHC class II costimulatory molecules as
well as the DC maturation marker DC-lysosome-associated membrane protein,
and they stimulate naive, allogeneic CD4(+) T cells efficiently, These two
DC subsets elicit distinct cytokine profiles in CD4(+) T cells, with the CD
11c(-) subset inducing higher levels of the Th2 cytokine IL-10, The differe
ntial mobilization of distinct DC subsets or DC precursors by in vivo admin
istration of FL and G-CSF offers a novel strategy to manipulate immune resp
onses in humans.