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IFN‐α promotes definitive maturation of dendritic cells generated by short‐term culture of monocytes with GM‐CSF and IL‐4
Author(s) -
Dauer Marc,
Schad Katharina,
Junkmann Jana,
Bauer Christian,
Herten Jan,
Kiefl Rosemarie,
Schnurr Max,
Endres Stefan,
Eigler Andreas
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1005592
Subject(s) - biology , dendritic cell , c c chemokine receptor type 7 , priming (agriculture) , immunology , microbiology and biotechnology , cd40 , cytokine , chemokine , t cell , chemokine receptor , immune system , cytotoxic t cell , in vitro , biochemistry , botany , germination
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)‐γ increased viability of DC and promoted definitive maturation as defined by maintenance of a mature phenotype after withdrawal of cytokines. Addition of IFN‐α to DC cultures prior to stimulation further enhanced definitive maturation: IFN‐α‐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‐α‐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‐α in DC development: IFN‐α priming of monocytes promotes definitive maturation of DC upon activation.