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Departments of
* Dermatology and
Internal Medicine, University of Innsbruck, Innsbruck, Austria
Dendritic cells (DC) derived from plasmacytoid precursors depend on
IL-3 for survival and proliferation in culture, and they induce
preferentially Th2 responses. Monocytes express not only GM-CSF
receptors, but also IL-3Rs. Therefore, we examined whether IL-3 had an
effect on the functional plasticity of human monocyte-derived DC
generated in a cell culture system that is widely used in
immunotherapy. DC were generated with IL-3 (instead of GM-CSF) and
IL-4. Yields, maturation, phenotype (surface markers and Toll-like
receptors), morphology, and immunostimulatory capacity were similar.
Only CD1a was differentially expressed, being absent on IL-3-treated
DC. In response to CD40 ligation DC generated in the presence of IL-3
secreted significantly less IL-12 p70 and more IL-10 compared with DC
grown with GM-CSF. Coculture of naive allogeneic CD4+ T
cells with DC generated in the presence of IL-3 induced T cells to
produce significantly more IL-5 and IL-4 and less IFN-
compared with
stimulation with DC generated with GM-CSF. These data extend the
evidence that different cytokine environments during differentiation of
monocyte-derived DC can modify their Th cell-inducing properties. A
hitherto unrecognized effect of IL-3 on DC was defined, namely
suppression of IL-12 secretion and a resulting shift from Th1 toward
Th2.
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