We have shown previously that dendritic cells (DC) produce IL-12 upon interaction with CD4+ T cells. Here we ask how this IL-12 production is induced and regulated. Quantitative PCR and in situ hybridization for IL-12 p40 and an ELISA specific for the p70 heterodimer were used to determine IL-12 production. We demonstrate that ligation of either CD40 or MHC class II molecules independently trigger IL-12 production in DC, and that IL-12 production is downregulated by IL-4 and IL-10. The levels of bioactive IL-12 that can be released by triggering with an anti-CD40 mAb or with a T cell hybridoma are high (range 260-4700 pg/ml from 1 X 10(6) DC in 72 h). The CD40-mediated pathway indicates that IL-12 production is induced in DC upon interaction with activated, CD40 ligand-expressing helper T cells, even in the absence of cognate antigen recognition. Side-by-side comparison of IL-12 production, and blocking experiments employing an anti-CD40 ligand mAb, suggest that the CD40-mediated pathway is quantitatively more significant than induction via the MHC class II molecule. The importance of the CD40/CD40 ligand interaction for IL-12 induction in DC likely contributes to the recent finding that mice lacking the CD40 ligand are impaired in mounting Th1 type cell-mediated immune responses.
Article|
August 01 1996
High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.
F Koch,
F Koch
Department of Dermatology, University of Innsbruck, Austria.
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U Stanzl,
U Stanzl
Department of Dermatology, University of Innsbruck, Austria.
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P Jennewein,
P Jennewein
Department of Dermatology, University of Innsbruck, Austria.
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K Janke,
K Janke
Department of Dermatology, University of Innsbruck, Austria.
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C Heufler,
C Heufler
Department of Dermatology, University of Innsbruck, Austria.
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E Kämpgen,
E Kämpgen
Department of Dermatology, University of Innsbruck, Austria.
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N Romani,
N Romani
Department of Dermatology, University of Innsbruck, Austria.
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G Schuler
G Schuler
Department of Dermatology, University of Innsbruck, Austria.
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F Koch
Department of Dermatology, University of Innsbruck, Austria.
U Stanzl
Department of Dermatology, University of Innsbruck, Austria.
P Jennewein
Department of Dermatology, University of Innsbruck, Austria.
K Janke
Department of Dermatology, University of Innsbruck, Austria.
C Heufler
Department of Dermatology, University of Innsbruck, Austria.
E Kämpgen
Department of Dermatology, University of Innsbruck, Austria.
N Romani
Department of Dermatology, University of Innsbruck, Austria.
G Schuler
Department of Dermatology, University of Innsbruck, Austria.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (2): 741–746.
Citation
F Koch, U Stanzl, P Jennewein, K Janke, C Heufler, E Kämpgen, N Romani, G Schuler; High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.. J Exp Med 1 August 1996; 184 (2): 741–746. doi: https://doi.org/10.1084/jem.184.2.741
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