Regulatory Th2 response induced following adoptive transfer of dendritic cells in prediabetic NOD mice

Eur J Immunol. 2002 Jul;32(7):2021-30. doi: 10.1002/1521-4141(200207)32:7<2021::AID-IMMU2021>3.0.CO;2-J.

Abstract

We previously demonstrated that immunotherapy with dendritic cells (DC) prevented diabetes development in prediabetic NOD mice and that this effect was optimal when using a stimulatory DC population generated from bone marrow cells cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. In this study, we have investigated the mechanism by which GM-CSF- and IL-4-cultured DC prevent diabetes in prediabetic NOD mice. Histological analysis of pancreatic tissue from DC-treated mice revealed a reduction in the severity of insulitis compared to controls. Analysisof the T cell response in DC-treated mice suggested a general shift towards a Th2-dominated response, as determined by cytokine production following either concanavalin A or anti-TCR stimulation. Furthermore, sorted CD45RB(lo) CD25+ CD4+ T cells from the spleen of DC-treated mice produced high amounts of Th2 cytokines following anti-TCR stimulation, suggesting that these cells are responsible for the apparent Th2 shift. We conclude that DC therapy may have corrected the immunoregulatory defect in the NOD mouse, thus restoring a balance between pathogenic Th1 cells and protective Th2 cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / biosynthesis
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control
  • Diabetes Mellitus, Type 1 / therapy
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Immunotherapy, Adoptive* / methods
  • Interleukin-4 / immunology*
  • Interleukin-4 / pharmacology
  • Leukocyte Common Antigens / immunology
  • Mice
  • Mice, Inbred NOD
  • Pancreas / immunology*
  • Pancreas / pathology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Receptors, Interleukin-2 / immunology
  • Th2 Cells / immunology*

Substances

  • Biomarkers
  • Cytokines
  • Receptors, Interleukin-2
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1