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

Abstract

Abstract It was observed that interferon β (IFN-β) prevents the down-regulation of the interleukin-3 receptor α chain (IL-3Rα), which spontaneously occurs during culture of human monocytes. The functionality of IL-3R was demonstrated by the fact that IL-3 rescued IFN-β–treated monocytes from apoptosis. Monocytes cultured in the presence of IFN-β 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-β and IL-3 secreted high levels of IL-6, IL-8, and tumor necrosis factor-α 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-β DCs induced a vigorous proliferative response of allogeneic cord blood T cells and elicited the production of high levels of IFN-γ and IL-5 by naive adult CD4+ T cells. Finally, IL-3–IFN-β DCs were found to produce much higher levels of IFN-α 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-β differentiate into DCs with potent helper T-cell stimulatory capacity despite their low secretion of IL-12.