IFN-alpha enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells

Luft, T; Luetjens, P; Hochrein, H; Toy, T; Masterman, KA; Rizkalla, M; Maliszewski, C; Shortman, K; Cebon, J; Maraskovsky, E

Author(s): Luft, T; Luetjens, P; Hochrein, H; Toy, T; Masterman, KA; Rizkalla, M; Maliszewski, C; Shortman, K; Cebon, J; Maraskovsky, E;
Details: Publication Year 2002-04,Volume 14,Issue #4,Page 367-380
Journal Title: INTERNATIONAL IMMUNOLOGY
Publication Type: Journal Article
Abstract: Type I IFN are immune modulatory cytokines that are secreted during early stages of infection. Type I IFN bridge the innate and the adaptive immune system in humans and mice. We compared the capacity of type I and II IFN to induce the functional maturation of monocyte-derived dendritic cells (MoDC). Extending our earlier observation that type I IFN promote DC maturation, we report that these cytokines also enhance DC differentiation by augmenting CD40 ligand (CD40L)-induced cytokine secretion by MoDC. Type I IFN alone were poor inducers of MoDC maturation as compared with other stimuli. They up-regulated the expression of HLA-DR, CD80, CD86, partially CCR7 but not CD83, partially reduced antigen-uptake function, increased the levels of IL-12p35 mRNA, and prolonged surface expression of peptide-MHC class I complexes for presentation to cytotoxic T lymphocytes, but did not induce migration towards CCL21 chemokine. However, type I IFN were potent co-factors for CD40L-mediated function. Here, they enhanced CD40L-mediated IL-6, IL-10 and IL-12p70 secretion. Furthermore, when combined with IL-1beta and/or IL-4, IFN-alpha2a type I IFN increased CD40L-mediated IL-12p70 production by 2- to 3-fold, and biased the IL-12 p40/p70 ratio towards the IFN-gamma inducing p70 heterodimer, this correlating with higher levels of IFN-gamma secretion by allogeneic T cell subsets and NK cells. Our results suggest that the rapid expression of CD40L, IFN and IL-1beta at sites of infection and inflammation can act in concert on immature DC, thereby linking innate and adaptive immune responses. In this way, type I IFN play a dual role as DC maturation factors and enhancers of CD40L-mediated DC activation.
Publisher: OXFORD UNIV PRESS
Keywords: SMOOTH-MUSCLE CELLS; PROTEIN MESSENGER-RNA; HERPES-SIMPLEX VIRUS; HUMAN T-CELLS; INTERFERON-ALPHA; IN-VITRO; IL-12 PRODUCTION; MURINE MACROPHAGES; RECEPTOR COMPONENT; ENDOTHELIAL-CELLS
Publisher's Version: https://doi.org/10.1093/intimm/14.4.367
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2002-04-01 12:00:00