Monocyte-derived CD1a(+) and CD1a(-) dendritic cell subsets differ in their cytokine production profiles, susceptibilities to transfection, and capacities to direct Th cell differentiation

We describe a phenotypically and functionally novel monocyte-derived dendri tic cell (DC) subset, designated mDC2, that lacks IL-12 synthesis, produces high levels of IL-10, and directs differentiation of Th0/Th2 cells. Like c onventional monocyte-derived DC, designated mDC1, mDC2 expressed high level s of CD11c, CD40, CD80, CD86, and MHC class II molecules. However, in contr ast to mDC1, mDC2 lacked expression of CD1a, suggesting an association betw een cytokine production profile and CD1a expression in DC. mDC2 could be ma tured into CD83(+) DC cells in the presence of anti-CD40 mAbs and LPS plus IFN-gamma but they remained CD1a(-) and lacked IL-12 production even upon m aturation. The lack of IL-12 and CD1a expression by mDC2 did not affect the ir APC capacity, because mDC2 stimulated MLR to a similar degree as mDC1, H owever, while mDC1 strongly favored Th1 differentiation, mDC2 directed diff erentiation 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 v ectors was significantly higher than that of mDC1, and therefore mDC2 may p rovide improved means to manipulate Ag-specific T cell responses after tran sfection ex vivo. Taken together, these data indicate that peripheral blood monocytes have the capacity to differentiate into DC subsets with differen t cytokine production profiles, which is associated with altered capacity t o direct Th cell differentiation.