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

Hum Gene Ther. 2003 Jan 1;14(1):13-23. doi: 10.1089/10430340360464679.


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.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antigens, CD / metabolism
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • CD40 Antigens / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / physiology*
  • Dendritic Cells / virology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Female
  • Genetic Therapy / methods*
  • Interferon-gamma / pharmacology
  • Interleukin-4 / genetics*
  • Interleukin-4 / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred NOD
  • Pancreas / metabolism
  • Pancreatitis / therapy*
  • Phantoms, Imaging
  • Spleen / immunology
  • Spleen / physiology
  • T-Lymphocytes / physiology
  • Th2 Cells / metabolism
  • Th2 Cells / physiology
  • Transduction, Genetic


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • Cd86 protein, mouse
  • Cytokines
  • Membrane Glycoproteins
  • Interleukin-4
  • Interferon-gamma