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Maxygen, Redwood City, CA 94063
We describe a phenotypically and functionally novel
monocyte-derived dendritic cell (DC) subset, designated mDC2, that
lacks IL-12 synthesis, produces high levels of IL-10, and directs
differentiation of Th0/Th2 cells. Like conventional monocyte-derived
DC, designated mDC1, mDC2 expressed high levels of CD11c, CD40, CD80,
CD86, and MHC class II molecules. However, in contrast to mDC1, mDC2
lacked expression of CD1a, suggesting an association between cytokine
production profile and CD1a expression in DC. mDC2 could be matured
into CD83+ DC cells in the presence of anti-CD40 mAbs
and LPS plus IFN-
, but they remained CD1a- and lacked
IL-12 production even upon maturation. The lack of IL-12 and CD1a
expression by mDC2 did not affect their APC capacity, because mDC2
stimulated MLR to a similar degree as mDC1. However, while mDC1
strongly favored Th1 differentiation, mDC2 directed differentiation of
Th0/Th2 cells when cocultured with purified human peripheral blood T
cells, further indicating functional differences between mDC1 and mDC2.
Interestingly, the transfection efficiency of mDC2 with plasmid DNA
vectors was significantly higher than that of mDC1, and therefore mDC2
may provide improved means to manipulate Ag-specific T cell responses
after transfection ex vivo. Taken together, these data indicate that
peripheral blood monocytes have the capacity to differentiate into DC
subsets with different cytokine production profiles, which is
associated with altered capacity to direct Th cell
differentiation.
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