Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) cell–inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human thymic DCs, and cultured human monocyte-derived DCs. IL-12 production required both a microbial or T cell–derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cytokines present rather than the stimulus used. IL-4 alone or together with granulocyte/macrophage colony-stimulating factor or interferon γ effectively enhanced the production of the bioactive heterodimer and selectively reduced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-driving cytokine, provides a negative feedback causing DCs to produce the major Th1-inducing cytokine, bioactive IL-12.
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18 September 2000
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September 11 2000
Interleukin (Il)-4 Is a Major Regulatory Cytokine Governing Bioactive IL-12 Production by Mouse and Human Dendritic Cells
Hubertus Hochrein,
Hubertus Hochrein
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
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Meredith O'Keeffe,
Meredith O'Keeffe
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
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Thomas Luft,
Thomas Luft
bLudwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
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Stéphane Vandenabeele,
Stéphane Vandenabeele
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
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Raelene J. Grumont,
Raelene J. Grumont
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
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Eugene Maraskovsky,
Eugene Maraskovsky
bLudwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
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Ken Shortman
Ken Shortman
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
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Hubertus Hochrein
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
Meredith O'Keeffe
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
Thomas Luft
bLudwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
Stéphane Vandenabeele
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
Raelene J. Grumont
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
Eugene Maraskovsky
bLudwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
Ken Shortman
aFrom The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
Abbreviations used in this paper: BSS, balanced salt solution; DC, dendritic cell; MoDC, monocyte-derived DC; poly I:C, polyinosinic-polycytidylic acid; SAC, Staphylococcus aureus Cowan I.
Received:
May 01 2000
Revision Requested:
July 17 2000
Accepted:
July 19 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 192 (6): 823–834.
Article history
Received:
May 01 2000
Revision Requested:
July 17 2000
Accepted:
July 19 2000
Citation
Hubertus Hochrein, Meredith O'Keeffe, Thomas Luft, Stéphane Vandenabeele, Raelene J. Grumont, Eugene Maraskovsky, Ken Shortman; Interleukin (Il)-4 Is a Major Regulatory Cytokine Governing Bioactive IL-12 Production by Mouse and Human Dendritic Cells. J Exp Med 18 September 2000; 192 (6): 823–834. doi: https://doi.org/10.1084/jem.192.6.823
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