title: A Human Cell Line Model for Interferon-α Driven Dendritic Cell Differentiation.
abstract: The CD34+ MUTZ-3 acute myeloid leukemia cell line has been used as a dendritic cell (DC) differentiation model. This cell line can be cultured into Langerhans cell (LC) or interstitial DC-like cells using the same cytokine cocktails used for the differentiation of their primary counterparts. Currently, there is an increasing interest in the study and clinical application of DC generated in the presence of IFNα, as these IFNα-DC produce high levels of inflammatory cytokines and have been suggested to be more potent in their ability to cross-present protein antigens, as compared to the more commonly used IL-4-DC. Here, we report on the generation of IFNα-induced MUTZ-DC. We show that IFNα MUTZ-DC morphologically and phenotypically display characteristic DC features and are functionally equivalent to "classic" IL-4 MUTZ-DC. IFNα MUTZ-DC ingest exogenous antigens and can subsequently cross-present HLA class-I restricted epitopes to specific CD8+ T cells. Importantly, mature IFNα MUTZ-DC express CCR7, migrate in response to CCL21, and are capable of priming naïve antigen-specific CD8+ T cells. In conclusion, we show that the MUTZ-3 cell line offers a viable and sustainable model system to study IFNα driven DC development and functionality.
authors.affiliation: Dept of Hematology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Jurjen M
authors.initials: JM
authors.lastname: Ruben
authors.affiliation: Dept of Hematology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Lindy L
authors.initials: LL
authors.lastname: Visser
authors.affiliation: Dept of Hematology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Kimberley M
authors.initials: KM
authors.lastname: Heinhuis
authors.affiliation: Dept of Molecular Cell Biology and Immunology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: O'Toole
authors.affiliation: Dept of Hematology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
authors.affiliation: Dept of Hematology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Theresia M
authors.initials: TM
authors.lastname: Westers
authors.affiliation: Dept of Hematology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.affiliation: Dept of Medical Oncology, VU University medical center-Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.affiliation: Dept of Hematology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D045744:Cell Line, Tumor / Q000166:cytology*; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D000939:Epitopes / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D010641:Phenotype
chemical_list: D018952:Antigens, CD34; D019013:CD40 Antigens; D016207:Cytokines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor