Ifn-alpha Promotes Definitive Maturation of Dendritic Cells Generated by Short-term Culture of Monocytes with Gm-csf and Il-4.
From: Section of Gastroenterology and Division Clinical Pharmacology, Medizinische Klinik Innenstadt, University of Munich, Munich, Germany.
Journal of leukocyte biology
- Publish Date: Aug 2006
- ISSN: 0741-5400
- Volume: 80
- Issue: 2
- Pages: 278-86
- Medium: Print
- Language: English
- Citation (JAMA): Dauer Marc, Schad Katharina, Junkmann Jana, et al. Ifn-alpha Promotes Definitive Maturation of Dendritic Cells Generated by Short-term Culture of Monocytes with Gm-csf and Il-4.. J. Leukoc. Biol. Aug 2006;80:278-86
Abstract
Dendritic cells (DC) generated in vitro have to be viable and phenotypically mature to be capable of inducing T cell-mediated immunity after in vivo administration. To facilitate optimization of DC-based vaccination protocols, we investigated whether the cytokine environment and the mode of activation affect maturation and survival of DC derived from monocytes by a short-term protocol. Monocytes cultured for 24 h with granulocyte macrophage-colony stimulating factor and interleukin-4 were stimulated with proinflammatory mediators for another 36 h to generate mature DC. Additional activation with CD40 ligand and interferon (IFN)-gamma increased viability of DC and promoted definitive maturation as defined by maintenance of a mature phenotype after withdrawal of cytokines. Addition of IFN-alpha to DC cultures prior to stimulation further enhanced definitive maturation: IFN-alpha-primed DC expressed high levels of costimulatory molecules and CC chemokine receptor 7 (CCR7) up to 5 days after cytokine withdrawal. Compared with unprimed DC, IFN-alpha-primed DC displayed equal capacity to migrate upon CCR7 ligation and to prime antigen-specific T helper cell as well as cytolytic T cell responses. In conclusion, we show that optimal maturation and survival of monocyte-derived DC require multiple activation signals. Furthermore, we identified a novel role for IFN-alpha in DC development: IFN-alpha priming of monocytes promotes definitive maturation of DC upon activation.
Mesh Headings (Keywords): CD40 Ligand, Cell Differentiation, Cell Movement, Cells, Cultured, Dendritic Cells, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Interferon Type II, Interferon-alpha, Interleukin-12, Interleukin-4, Monocytes, Receptors, CCR7, Receptors, Chemokine, T-Lymphocytes, T-Lymphocytes, Cytotoxic
Check for Full Text / PubMed Unique Identifier (PMID): 16769767
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