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A Human Cell Line Model for Interferon-α Driven Dendritic Cell Differentiation

  • Jurjen M. Ruben
  • , Lindy L. Visser
  • , Kimberley M. Heinhuis
  • , Tom O'Toole
  • , Hetty J. Bontkes
  • , Theresia M. Westers
  • , Gert J. Ossenkoppele
  • , Tanja D. De Gruijl
  • , Arjan A. Van De Loosdrecht

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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 crosspresent 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 naíve 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.

Original languageEnglish
Article numbere0135219
JournalPloS one
Volume10
Issue number8
DOIs
Publication statusPublished - 7 Aug 2015
Externally publishedYes

Keywords

  • Antigens, CD34/metabolism
  • CD40 Antigens/metabolism
  • CD8-Positive T-Lymphocytes/cytology
  • Cell Differentiation
  • Cell Line, Tumor/cytology
  • Cell Movement
  • Cytokines/metabolism
  • Dendritic Cells/cytology
  • Epitopes/metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
  • Histocompatibility Antigens Class I/metabolism
  • Humans
  • Interferon-alpha/pharmacology
  • Interleukin-4/pharmacology
  • Leukemia, Myeloid, Acute/metabolism
  • Phenotype

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