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Blood, 1 February 2002, Vol. 99, No. 3, pp. 993-998
IMMUNOBIOLOGY
Interleukin-3 and interferon  cooperate to induce
differentiation of monocytes into dendritic cells with potent helper
T-cell stimulatory properties
Christel Buelens,
Emmanuel
J. Bartholomé,
Zoulikha Amraoui,
Michael Boutriaux,
Isabelle Salmon,
Kris Thielemans,
Fabienne Willems, and
Michel Goldman
From the Laboratory of Experimental Immunology and the
Laboratory of Anatomo-Pathology, Université Libre de Bruxelles,
and the Laboratory of Physiology-Immunology, Vrije Universiteit
Brussel, Brussels, Belgium.
It was observed that interferon  (IFN-) prevents the
down-regulation of the interleukin-3 receptor  chain (IL-3R),
which spontaneously occurs during culture of human monocytes. The
functionality of IL-3R was demonstrated by the fact that IL-3 rescued
IFN--treated monocytes from apoptosis. Monocytes cultured in the
presence of IFN- and IL-3 acquire a dendritic morphology and express
high levels of HLA antigen class I and class II and costimulatory
molecules. When stimulated by either lipopolysaccharide or fibroblasts
expressing CD40 ligand (CD40L) transfectants, dendritic cells (DCs)
generated in IFN- and IL-3 secreted high levels of IL-6, IL-8, and
tumor necrosis factor- but low levels of IL-12 in comparison with
DCs generated in IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In mixed leukocyte culture, IL-3-IFN- DCs induced a vigorous proliferative response of allogeneic cord blood T
cells and elicited the production of high levels of IFN- and IL-5 by naive adult CD4+ T cells. Finally, IL-3-IFN- DCs were
found to produce much higher levels of IFN- than IL-4-GM-CSF DCs in
response to Poly (I:C) but not to influenza virus. It was concluded
that monocytes cultured in the presence of IL-3 and IFN-
differentiate into DCs with potent helper T-cell stimulatory capacity
despite their low secretion of IL-12.
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