IL-4 Triggers Autoimmune Diabetes by Increasing Self-Antigen Presentation Within the Pancreatic Islets

Clin Immunol. 2001 Feb;98(2):190-9. doi: 10.1006/clim.2000.4979.

Abstract

Several findings have recently questioned the long held hypothesis that cytokines belonging to the Th2 pathway are protective in T-cell-mediated autoimmunity. Among them, there is our previous report that pancreatic expression of IL-4 activated islet antigen-specific BDC2.5 T cells and rendered them able to trigger insulin-dependent diabetes mellitus in ins-IL-4/BDC2.5 mice (Mueller et al., Immunity, 7, 1997). Here we analyze the mechanisms underlying IL-4-mediated activation of the self-reactive BDC2.5 T cells. IL-4 is mainly known as the Th2-driving cytokine. However, IL-4 is also critical for DC maturation and upregulation of antigen uptake and presentation by macrophages. In our model, we found that pancreatic expression of IL-4 activated self-reactive BDC2.5 T cells by increasing islet antigen presentation by macrophages and dendritic cells. IL-4 could have triggered self-antigen presentation within the pancreatic islets both by driving maturation of DC from a tolerizing to a priming state and by increasing self-antigen uptake by macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / drug effects*
  • Autoantigens / immunology*
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • B-Lymphocytes / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Immune Tolerance / physiology
  • Interleukin-4 / pharmacology
  • Interleukin-4 / toxicity*
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Models, Immunological
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / toxicity
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology

Substances

  • Autoantigens
  • Recombinant Proteins
  • Interleukin-4