Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice

Clin Exp Immunol. 2003 Dec;134(3):388-95. doi: 10.1111/j.1365-2249.2003.02308.x.


CD11c+/CD11b+dendritic cells (DC) with high levels of major histocompatibility complex (MHC) class II and co-stimulatory molecules have been derived from spleen cells cultured with granulocyte-macrophage colony stimulating factor (GM-CSF) + flt-3L + interleukin (IL)-6 (flt-3L-DC). Investigating in vivo the function of DC in non-obese diabetic mice (NOD), we showed that a single injection of this in vitro-derived subset of DC prevents the development of diabetes into prediabetic female mice. In contrast, DC derived from bone marrow cells cultured with GM-CSF + IL-4 [bone marrow (BM)-DC] induced no protection. Moreover, protection against diabetes following injection of flt-3L-DC was associated with IL-4 and IL-10 production in the spleen and the pancreatic lymph nodes of recipient mice, indicating that this DC population is able to polarize the immune response towards a Th2 pathway. As we shown previously, NOD BM-DC exhibit an enhanced capacity to produce IL-12p70 in response to lipopolysaccharide (LPS) and anti-CD40 stimulation compared to BM-DC from control mice. In contrast, NOD flt-3L-DC, as their control mouse counterpart, produced no IL-12p70 to these stimuli. Our findings show that a subset of DC, characterized by a mature phenotype and the absence of IL-12p70 production can be derived from NOD mouse spleen favouring IL-4 and IL-10 regulatory responses and protection from diabetes development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / prevention & control*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Immunotherapy, Adoptive / methods*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / immunology
  • Interleukins / biosynthesis*
  • Interleukins / immunology
  • Lymph Nodes / immunology
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred NOD
  • Spleen / immunology*


  • Interleukins
  • Membrane Proteins
  • flt3 ligand protein
  • Interleukin-10
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor