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Title: IFN-alpha enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells.
Austin Authors: Luft, Thomas;Luetjens, Petra;Hochrein, Hubertus;Toy, Tracey;Masterman, Kelly-Anne;Rizkalla, Mark;Maliszewski, Charlie;Shortman, Ken;Cebon, Jonathan S ;Maraskovsky, Eugene
Affiliation: Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
Issue Date: 1-Apr-2002
Publication information: International Immunology; 14(4): 367-80
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.
Gov't Doc #: 11934873
Journal: International immunology
Type: Journal Article
Subjects: Adjuvants, Immunologic.genetics.metabolism
Antigen Presentation
Antigens, Neoplasm
CD40 Ligand.metabolism
Cell Differentiation
Cell Movement
Cells, Cultured
Dendritic Cells.drug effects.metabolism
Granulocyte-Macrophage Colony-Stimulating Factor.metabolism
Interleukin-12 Subunit p35
Killer Cells, Natural.secretion
MART-1 Antigen
Neoplasm Proteins.metabolism
Protein Conformation
Protein Subunits
Appears in Collections:Journal articles

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