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Prevention of diabetes in NOD nice by administration of dendritic cells deficient in nuclear transcription factor-kappa B activity

Academic Article
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Overview

authors

  • Ma, L. L.
  • Qian, S. G.
  • Liang, X. Y.
  • Wang, L. F.
  • Woodward, J. E.
  • Giannoukakis, N.
  • Robbins, Paul D.
  • Bertera, S.
  • Trucco, M.
  • Fung, J. J.
  • Lu, L.

publication date

  • August 2003

journal

  • Diabetes  Journal

abstract

  • Abnormalities of dendritic cells (DCs) have been identified in type 1 diabetic patients and in nonobese diabetic (NOD) mice that are associated with augmented nuclear transcription factor (NF)-kappaB activity. An imbalance that favors development of the immunogenic DCs may predispose to the disease, and restoration of the balance by administration of DCs deficient in NF-kappaB activity may prevent diabetes. DCs propagated from NOD mouse bone marrow and treated with NF-kappaB-specific oligodeoxyribonucleotide (ODN) in vitro (NF-kappaB ODN DC) were assessed for efficacy in prevention of diabetes development in vivo. Gel shift assay with DC nuclear extracts confirmed specific inhibition of NF-kappaB DNA binding by NF-kappaB ODN. The costimulatory molecule expression, interleukin (IL)-12 production, and immunostimulatory capacity in presenting allo- and islet-associated antigens by NF-kappaB ODN DC were significantly suppressed. NF-kappaB ODN renders DCs resistant to lipopolysaccharide stimulation. Administration of 2 x 10(6) NF-kappaB ODN DCs into NOD mice aged 6-7 weeks effectively prevented the onset of diabetes. T-cells from pancreatic lymph nodes of NF-kappaB ODN DC-treated animals exhibited hyporesponsiveness to islet antigens with low production of interferon-gamma and IL-2. These findings provide novel insights into the mechanisms of autoimmune diabetes and may lead to development of novel preventive strategies.

subject areas

  • Animals
  • Antigen Presentation
  • Cytokines
  • DNA
  • Dendritic Cells
  • Diabetes Mellitus, Type 1
  • Female
  • Islets of Langerhans
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred NOD
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Phenotype
  • T-Lymphocytes
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Identity

International Standard Serial Number (ISSN)

  • 0012-1797

Digital Object Identifier (DOI)

  • 10.2337/diabetes.52.8.1976

PubMed ID

  • 12882913
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Additional Document Info

start page

  • 1976

end page

  • 1985

volume

  • 52

issue

  • 8

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