Signals required for differentiating dendritic cells from human monocytes in vitro.

Human peripheral blood monocytes (Mo) can quantitatively be differentiated into potent accessory cells which exhibit dendritic cell (DC) function and phenotype. This alternative differentiation of Mo into DC rather than into macrophages (M phi) will be triggered when signals leading to M phi differentiation are omitted from the culture. Serum contains such stimulatory signals and was therefore omitted from the cultures. The cells were cultured on solid agarose surfaces. This newly developed technique allows for the attachment-free differentiation of DC. In the absence of signals, Mo do not survive in culture. IL-1 and IL-6 are endogenously produced by Mo and create an autokrine stimulatory milieu which increases the accessory function. However, also mature Mph will respond by an increased accessory activity upon stimulation by these cytokines. Cyclic AMP is the most likely second messenger to trigger an increase in accessory activity. IL-4 plus GM-CSF further act to upregulate dendritic cell properties and function. By action of these mediators, virtually all markers and functions of Mo/M phi are lost, and the cells convert to the phenotype and function of dendritic cells.