The Journal of Experimental Medicine
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Published online 18 September 2000.
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© The Rockefeller University Press, 0022-1007/2000/9/823/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 6, September 18, 2000 823-834

Original Article

Interleukin (Il)-4 Is a Major Regulatory Cytokine Governing Bioactive IL-12 Production by Mouse and Human Dendritic Cells

Hubertus Hochreina, Meredith O'Keeffea, Thomas Luftb, Stéphane Vandenabeelea, Raelene J. Grumonta, Eugene Maraskovskyb, and Ken Shortmana

a From The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
b Ludwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria 3050, Australia.61-3-9347-085261-3-9345-2531

shortman{at}wehi.edu.au

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 {gamma} 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.

Key Words: granulocyte/macrophage colony-stimulating factor • homodimeric interleukin 12 • T helper type 1 • T helper type 2 • interferon {gamma}

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.

© 2000 The Rockefeller University Press


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