Generation of high cross-presentation ability human dendritic cells by combination of interleukin 4, interferon β and GM-CSF

Dendritic cell (DC)-based immunotherapies have been utilized for the treatment of numerous diseases. However, the conventional generation strategies of DCs in vitro require 7 days and these DCs showed an unsatisfactory function, which prompted us to explore new approaches. We found that in vitro culture of human CD14⁺ cells, in the medium containing granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4, as well as interferon β (IFN-β) for 48 h, followed by the maturation stimuli of IL-1β and poly I:C for another 24 h can be differentiated into high cross-presentation ability DCs (G4B-DCs). These DCs express high levels of CD11c, CD86, and HLA-DR, producing a high level of tumor necrosis factor α (TNF-α). Of note, compared with the conventional DCs, G4B-DCs showed a higher ability to promote allogeneic naïve CD4⁺ T cell and CD8⁺ T cell proliferation and interferon (IFN)-γ production. These DCs also have the remarkable ability to induce Flu-M1-specific CD8⁺ T cells. In addition, we found that these G4B-DCs express partially the cDC1 phenotype. These data indicate that G4B-DC is unique and may provide a relatively rapid alternative method for potential clinical use.

IFN-β; IL-4; cDC1; cross-presentation; dendritic cell.