Lack of IL-12 signaling in human allergen-specific Th2 cells (1996)

Author(s): Hilkens CM, Messer G, Tesselaar K, van Rietschoten AG, Kapsenberg ML, Wierenga EA

  • : Lack of IL-12 signaling in human allergen-specific Th2 cells

Abstract: IL-12 is a powerful skewer of CD4+ T cell responses toward the Th1 phenotype by inducing IFN-gamma production in naive Th cells. In the present study we addressed the question of whether IL-12 can reverse established Th2 responses into Th1/Th0 responses by inducing IFN-gamma production in memory Th2 cells. To this aim, allergen-specific CD4+ T cell clones (TCC) were generated from the peripheral blood of three atopic patients, and their cytokine profiles were analyzed. The majority of these TCC exhibited a strongly polarized Th2 cytokine profile, and the production of IFN-gamma could not be induced by exogenous IL-12. Only those TCC with low IFN-gamma levels in the absence of IL-12 responded to IL-12 by additional enhancement of IFN-gamma production. The IL-12 nonresponsiveness of the Th2 clones was further evident by the total lack of IL-12-induced phosphorylation of STAT4 (signal transducer and activator of transcription-4), a transcription factor that is typically involved in IL-12 signaling. Consequently, IL-12 also failed to induce the DNA-binding activity of STAT4-containing complexes in the nuclei of these Th2 clones. All TCC expressed equal levels of the low-affinity IL-12R beta1 subunit. Our results indicate that human allergen-specific Th cells with strongly polarized Th2 cytokine profiles do not respond to IL-12 and, therefore, cannot be induced to produce IFN-gamma. The apparent high frequency of IL-12-nonresponsive Th cells within the allergen-specific populations in atopic patients predicts a limited skewing potential of IL-12 in the case of established Th2 responses, but only affecting newly recruited naive Th cells.

Notes: 0022-1767 Journal Article

  • Short Title: Lack of IL-12 signaling in human allergen-specific Th2 cells
  • Date: 15-11-1996
  • Journal: Journal of Immunology
  • Volume: 157
  • Issue: 10
  • Pages: 4316-4321
  • Publisher: American Association of Immunologists
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Allergens/*immunology Antigens, Dermatophagoides Base Sequence/genetics Clone Cells DNA-Binding Proteins/agonists/biosynthesis Glycoproteins/immunology Human Interferon Type II/agonists/biosynthesis Interleukin-12/*deficiency/*pharmacology Receptors, Interleukin/analysis/biosynthesis Signal Transduction/*immunology Support, Non-U.S. Gov't T-Lymphocytes, Helper-Inducer/drug effects/immunology/metabolism Th2 Cells/*drug effects/immunology/*metabolism Trans-Activators/agonists/biosynthesis


Dr Catharien Hilkens
Reader in Immunotherapy