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Interferon‐α and granulocyte‐macrophage colony‐stimulating factor differentiate peripheral blood monocytes into potent antigen‐presenting cells

The diverse roles of interferon‐α (IFN‐α) in regulating the immune response to infectious agents suggested that it might affect dendritic cell (DC) development. Peripheral blood mononuclear cells cultured with IFN‐α and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) developed a dendritic morphology and expressed high levels of the class I and II human leukocyte antigens (HLA), B7 costimulatory molecules, adhesion proteins, and CD40. Elevated DC expression of B7‐2 and HLA‐DR was observed with increasing IFN‐α concentrations up to 5000 U/mL. The effects of IFN‐α on DC immunophenotype were not reversed by adding neutralizing antibodies against interleukin‐4 (IL‐4) or tumor necrosis factor α to the cell cultures or by eliminating lymphocytes from the cultures. The addition of IFN‐α to cultures containing optimal concentrations of IL‐4 and GM‐CSF significantly increased the B7‐2 and HLA‐DR levels above those present on DCs grown in two cytokines. The DCs generated with IFN‐α and GM‐CSF were potent antigen‐presenting cells in allogeneic mixed leukocyte reactions. They also were capable of taking up, processing, and presenting tetanus toxin to autologous T lymphocytes. These results demonstrate an important role for IFN‐α in the generation of DCs with potent antigen‐presenting capabilities from peripheral blood monocytes. J. Leukoc. Biol. 64: 358–367; 1998.