IL-4 is a mediator of IL-12p70 induction by human Th2 cells: reversal of polarized Th2 phenotype by dendritic cells

  • Kalinski P
  • Smits H
  • Schuitemaker J
 et al. 
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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

Author-supplied keywords

  • Adjuvants,Immunologic
  • Antigens
  • Antigens,CD40
  • Autoimmunity
  • B-Cell
  • Biology
  • CD40
  • CD40 Ligand
  • Cell Communication
  • Cells
  • Cells,Cultured
  • Coculture
  • Coculture Techniques
  • Cytokines
  • Dendritic Cells
  • Drug Synergism
  • Glycoproteins
  • Human
  • Humans
  • Immunity
  • Immunologic
  • Immunophenotyping
  • Infection
  • Interferon Type II
  • Interleukin-12
  • Interleukin-4
  • Ligands
  • Macrophage Activation
  • Macrophages
  • Membrane Glycoproteins
  • Netherlands
  • Phenotype
  • Research
  • Research Support
  • Support
  • Th2 Cells
  • biosynthesis
  • immunology
  • metabolism
  • pharmacology
  • physiology

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  • P Kalinski

  • H H Smits

  • J H Schuitemaker

  • P L Vieira

  • Eijk M van

  • E C de Jong

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