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Published online before print June 12, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1005592

Received for publication October 19, 2005.
Revised February 27, 2006.
Accepted for publication April 13, 2006.

Article

IFN- promotes definitive maturation of dendritic cells generated by short-term culture of monocytes with GM-CSF and IL-4

Section of Gastroenterology and Division of Clinical Pharmacology, Medizinische Klinik Innenstadt, University of Munich, Germany

^@ To whom correspondence should be addressed. E-mail: Eigler{at}lmu.de.

	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)- increased viability of DC and promoted definitive maturation as defined by maintenance of a mature phenotype after withdrawal of cytokines. Addition of IFN- to DC cultures prior to stimulation further enhanced definitive maturation: IFN--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--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- in DC development: IFN- priming of monocytes promotes definitive maturation of DC upon activation.

Key Words: differentiation • viability • priming • T cells • vaccination • immunotherapy

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