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Dendritic cells transduced to express interleukin-4 prevent diabetes in nonobese diabetic mice with advanced insulitis

Academic Article
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Overview

authors

  • Feili-Hariri, M.
  • Falkner, D. H.
  • Gambotto, A.
  • Papworth, G. D.
  • Watkins, S. C.
  • Robbins, Paul D.
  • Morel, P. A.

publication date

  • 2003

journal

  • Human Gene Therapy  Journal

abstract

  • Our previous studies demonstrated that adoptive transfer of dendritic cells (DC) prevents diabetes in young nonobese diabetic (NOD) mice by inducing regulatory T(H)2 cells. In this report, as a means of treating NOD mice with more advanced insulitis, we infected DC with adenoviral vectors expressing interleukin (IL)-4 (Ad.IL-4), eGFP (Ad.eGFP), or empty vector (Ad psi 5). DC infected with any of the Ad vectors expressed higher levels of CD40, CD80, and CD86 molecules than uninfected DC and Ad.IL-4 DC produced IL-4 after lipopolysaccharide (LPS) and interferon (IFN)-gamma stimulation. Ad-infected DC efficiently stimulated allogeneic T cells, and cultures of T cells with Ad.IL-4 DC produced lower levels of IFN-gamma and marginally higher levels of IL-4. In vivo studies demonstrated that the Ad.eGFP DC trafficked to the pancreatic lymph nodes within 24 hr of intravenous administration, and could be visualized in the T cell areas of the spleen. The intrapancreatic IFN-gamma:IL-4 or IFN-gamma:IL-10 cytokine ratios were lower in 10-week-old mice treated with Ad.IL-4 DC, and these mice were significantly protected from disease. These results demonstrate, for the first time, that genetically modified DC can prevent diabetes in the context of advanced insulitis.

subject areas

  • Adenoviridae
  • Animals
  • Antigens, CD
  • Antigens, CD40
  • Antigens, CD80
  • Antigens, CD86
  • Cells, Cultured
  • Cytokines
  • Dendritic Cells
  • Diabetes Mellitus, Experimental
  • Female
  • Genetic Therapy
  • Interferon-gamma
  • Interleukin-4
  • Lymph Nodes
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred NOD
  • Pancreas
  • Pancreatitis
  • Phantoms, Imaging
  • Spleen
  • T-Lymphocytes
  • Th2 Cells
  • Transduction, Genetic
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Identity

International Standard Serial Number (ISSN)

  • 1043-0342

Digital Object Identifier (DOI)

  • 10.1089/10430340360464679

PubMed ID

  • 12573055
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Additional Document Info

start page

  • 13

end page

  • 23

volume

  • 14

issue

  • 1

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