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*
Baylor Institute for Immunology Research, Dallas, TX 75204; and
Immunex Corporation, Seattle, WA 98101
Dendritic cells (DCs) have a unique ability to stimulate naive T
cells. Recent evidence suggests that distinct DC subsets direct
different classes of immune responses in vitro and in vivo. In humans,
the monocyte-derived CD11c+ DCs induce T cells to produce
Th1 cytokines in vitro, whereas the CD11c- plasmacytoid T
cell-derived DCs elicit the production of Th2 cytokines. In this paper
we report that administration of either Flt3-ligand (FL) or G-CSF to
healthy human volunteers dramatically increases distinct DC subsets, or
DC precursors, in the blood. FL increases both the CD11c+
DC subset (48-fold) and the CD11c- IL-3R+ DC
precursors (13-fold). In contrast, G-CSF only increases the
CD11c- precursors (>7-fold). Freshly sorted
CD11c+ 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
IFN-
, in response to influenza virus. CD11c+ and
CD11c- cells can mature in vitro with GM-CSF + TNF- or
with IL-3 + CD40 ligand, respectively. 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 CD11c- subset inducing higher levels of the Th2
cytokine IL-10. The differential mobilization of distinct DC subsets or
DC precursors by in vivo administration of FL and G-CSF offers a novel
strategy to manipulate immune responses in humans.
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M. Gilliet, A. Boonstra, C. Paturel, S. Antonenko, X.-L. Xu, G. Trinchieri, A. O'Garra, and Y.-J. Liu The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating Factor J. Exp. Med., April 1, 2002; 195(7): 953 - 958. [Abstract] [Full Text] [PDF]
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