Altered dendritic cells (DC) might be responsible for regulatory T cell imbalance and autoimmunity in nonobese diabetic (NOD) mice

Eur Cytokine Netw. Jan-Mar 2002;13(1):29-37.

Abstract

Nonobese diabetic (NOD) mice spontaneously develop diabetes, an auto-immune disease characterized by the destruction of insulin-secreting beta-cells by autoreactive T cells. Defects in development and/or functions of dendritic cells (DC) might be critical in eliciting the auto-immune reaction to beta cells in this model. In this paper, DC differentiation in NOD mice was investigated in vitro using bone marrow-derived progenitors (BM-DC) in the presence of GM-CSF and IL-4 or spleen-derived progenitors in the presence of GM-CSF and early acting cytokines such as Flt-3L and IL-6 (SPL-DC). In both culture systems, the absolute number of NOD DC generated was strongly reduced as compared to control strains. In addition, both BM-DC and SPL-DC from NOD mice show defective differentiation into mature DC in conventional culture conditions as indicated by low expression of MHC class II and CD80 molecules among CD11c positive cells and low capacity to stimulate allogeneic T cells. However, DC achieved full maturation when exposed to LPS, except for MHC class II expression that remained decreased. Ex vivo analysis confirmed an unusual phenotype of NOD DC. Both sets of results are thus consistent with a specific defect of DC maturation in these mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • Bone Marrow Cells / cytology
  • Cell Count
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Cytokines / pharmacology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology*
  • Disease Models, Animal
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • In Vitro Techniques
  • Interleukin-12 / biosynthesis
  • Lipopolysaccharides / pharmacology*
  • Lymphocyte Culture Test, Mixed
  • Major Histocompatibility Complex / immunology
  • Major Histocompatibility Complex / physiology
  • Mice
  • Mice, Inbred NOD / immunology
  • Spleen / cytology
  • T-Lymphocytes / immunology*

Substances

  • B7-1 Antigen
  • Cytokines
  • Lipopolysaccharides
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor