IMMUNOBIOLOGY Interleukin-3 and interferon cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties

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 IFNand 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 IFNand IL-3 secreted high levels of IL-6, IL-8, and tumor necrosis factorbut low levels of IL-12 in comparison with DCs generated in IL-4 and granulocyte-macrophage colonystimulating factor (GM-CSF). In mixed leukocyte culture, IL-3–IFNDCs induced a vigorous proliferative response of allogeneic cord blood T cells and elicited the production of high levels of IFNand IL-5 by naive adult CD4 T cells. Finally, IL-3– IFNDCs were found to produce much higher levels of IFNthan 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 IFNdifferentiate into DCs with potent helper T-cell stimulatory capacity despite their low secretion of IL-12. (Blood. 2002;99:993-998)