Differential regulation of the Janus kinase-STAT pathway and biologic function of IL-13 in primary human NK and T cells: a comparative study with IL-4

J Immunol. 1998 Jul 1;161(1):218-27.

Abstract

IL-13, a cytokine similar to IL-4, is a regulator of human B cell and monocyte functions. Biologic effects of IL-13 on primary human NK and T cells have not been well defined. We demonstrate that, in primary NK cells, IL-13, but not IL-4, may induce low levels of IFN-gamma secretion. When NK cells were costimulated with IL-13 and IL-2, IL-13 generally resulted in two types of reactivity: IL-13 synergized with IL-2 to stimulate IFN-gamma production or it modestly inhibited IL-2-mediated IFN-gamma production. In both types of donors, the effect of IL-13 on IL-2-induced IFN-gamma production was in marked contrast to the strong inhibition seen with IL-4 in NK cells. Additionally, IL-13 suppresses IL-2-induced NK cytolytic and proliferative activities although less efficiently than IL-4. In T cells, IL-13 inhibits anti-CD3 mAb/IL-2- or PHA-mediated IFN-gamma production and enhances cytolytic potential. Furthermore, we demonstrate that IL-13, like IL-4, induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 (JAK3) in NK and T cells. We observed that Abs directed against unique domains of STAT6 have differential effects on complexes in T cells but not in NK cells, suggesting different STAT6 isoforms. These findings show that IL-13 and IL-4 have the ability to regulate NK and T cell activation and that IL-13 is a potent regulator of STAT6 and JAK3 in these cell types.

Publication types

  • Comparative Study

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cytotoxicity, Immunologic / drug effects
  • DNA-Binding Proteins / biosynthesis
  • Dose-Response Relationship, Immunologic
  • Growth Inhibitors / pharmacology
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-13 / pharmacology
  • Interleukin-13 / physiology*
  • Interleukin-2 / antagonists & inhibitors
  • Interleukin-2 / pharmacology
  • Interleukin-4 / physiology*
  • JNK Mitogen-Activated Protein Kinases
  • Killer Cells, Natural / enzymology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Lymphocyte Activation / drug effects
  • Macromolecular Substances
  • Mitogen-Activated Protein Kinases*
  • STAT6 Transcription Factor
  • Signal Transduction / immunology*
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Time Factors
  • Trans-Activators / biosynthesis
  • Trans-Activators / metabolism*

Substances

  • DNA-Binding Proteins
  • Growth Inhibitors
  • Interleukin-13
  • Interleukin-2
  • Macromolecular Substances
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Trans-Activators
  • Interleukin-4
  • Interferon-gamma
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases