IL-4 Is a Mediator of IL-12p70 Induction by Human Th2 Cells: Reversal of Polarized Th2 Phenotype by Dendritic Cells

IL-12 is a key inducer of Th1-associated inflammatory responses, protective against intracellular infections and cancer, but also involved in autoimmune tissue destruction. We report that human Th2 cells interacting with monocyte-derived dendritic cells (DC) effectively induce bioactive IL-12p70 and...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2000-08, Vol.165 (4), p.1877-1881
Main Authors: Kalinski, Pawel, Smits, Hermelijn H, Schuitemaker, Joost H. N, Vieira, Pedro L, van Eijk, Marco, de Jong, Esther C, Wierenga, Eddy A, Kapsenberg, Martien L
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - physiology
CD40 Antigens - metabolism
CD40 Ligand
Cell Communication - immunology
Cells, Cultured
Coculture Techniques
Dendritic Cells - immunology
Dendritic Cells - metabolism
Drug Synergism
Humans
Immunophenotyping
Interferon-gamma - physiology
Interleukin-12 - biosynthesis
Interleukin-12 - pharmacology
Interleukin-4 - physiology
Ligands
Macrophage Activation
Macrophages - immunology
Macrophages - metabolism
Membrane Glycoproteins - immunology
Th2 Cells - immunology
Th2 Cells - metabolism
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Summary:IL-12 is a key inducer of Th1-associated inflammatory responses, protective against intracellular infections and cancer, but also involved in autoimmune tissue destruction. We report that human Th2 cells interacting with monocyte-derived dendritic cells (DC) effectively induce bioactive IL-12p70 and revert to Th0/Th1 phenotype. In contrast, the interaction with B cells preserves polarized Th2 phenotype. The induction of IL-12p70 in Th2 cell-DC cocultures is prevented by IL-4-neutralizing mAb, indicating that IL-4 acts as a Th2 cell-specific cofactor of IL-12p70 induction. Like IFN-gamma, IL-4 strongly enhances the production of bioactive IL-12p70 heterodimer in CD40 ligand-stimulated DC and macrophages and synergizes with IFN-gamma at low concentrations of both cytokines. However, in contrast to IFN-gamma, IL-4 inhibits the CD40 ligand-induced production of inactive IL-12p40 and the production of either form of IL-12 induced by LPS, which may explain the view of IL-4 as an IL-12 inhibitor. The presently described ability of IL-4 to act as a cofactor of Th cell-mediated IL-12p70 induction may allow Th2 cells to support cell-mediated immunity in chronic inflammatory states, including cancer, autoimmunity, and atopic dermatitis.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.165.4.1877