Low levels of interferon-α induce CD86 (B7.2) expression and accelerates dendritic cell maturation from human peripheral blood mononuclear cells

Abstract

Interferon-α (IFN-α) (IFN-α2b) is an immunoregulatory cytokine that is presently used in a recombinant form for the treatment of tumours and chronic viral infection. However, its mechanism of action remains largely undefined. In this paper, we studied the effects of low doses of IFN-α (0- 100 U/ml) on the generation of dendritic cells with granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumour necrosis factor (TNF)-α in cultures of human peripheral blood mononuclear cells (PBMCs). An addition of IFN-α to the PBMC cultures greatly increased the HLA class II and the CD86 expression on developing dendritic cells (DCs) during a 7-day culture period. When added at the initiation of the PBMC culture, as little as 10 U/ml dramatically increased the HLA class II and CD86 expression, with maximal effects observed between 50 and 100 U/ml in all PBMC preparations tested. Almost all of the nonadherent cells induced with added IFN-α possessed a phenotype of mature DCs, being CD1a(low), CD83+, HLA class II(high), CD86(high), CD40(high), and CD80(low), while being negative for the monocyte/macrophage and lymphocyte markers. In contrast, the floating cells isolated from cultures grown without IFN-α were mostly immature DCs with a CD1a(high), CD83-, HLA class II(int/high), CD86(low/int), CD80(low) phenotype. An addition of 50 U/ml IFN-α at the time of the culture initiation greatly increased both the number of mature DCs generated and their rate of appearance; by 3 days of culture, many large floating aggregates were present containing mature CD83+, CD1a(low) DCs, while much fewer aggregates of mature DCs were found without added IFN-α. Histochemical staining confirmed that the floating cells induced with IFN-α had typical DC features, including irregularly shaped nuclei, few cytoplasmic granules, and absent or diffuse perinuclear staining for esterase. Our results suggest that IFN-α is a potent accelerator of DC maturation in vitro. These effects on DC maturation may explain its clinical success in the treatment of cancer and viral infection as well as its ability to promote autoimmunity.