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.
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.
Morin
J
J
Laboratoire d'Immunologie, Génétique et Traitement des Maladies Métaboliques et du Diabète, Inserm U 561, Hôpital Saint-Vincent-de-Paul, Paris, France.
Faideau
B
B
Gagnerault
M-C
MC
Lepault
F
F
Boitard
C
C
Boudaly
S
S
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D003920:Diabetes Mellitus / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000276:immunology*
D007378:Interleukins; D008565:Membrane Proteins; C084881:flt3 ligand protein; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor