Regulatory Th2 response induced following adoptive transfer of dendritic cells in prediabetic NOD mice.
We previously demonstrated that immunotherapy with dendritic cells (DC) prevented diabetes development in prediabetic NOD mice and that this effect was optimal when using a stimulatory DC population generated from bone marrow cells cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. In this study, we have investigated the mechanism by which GM-CSF- and IL-4-cultured DC prevent diabetes in prediabetic NOD mice. Histological analysis of pancreatic tissue from DC-treated mice revealed a reduction in the severity of insulitis compared to controls. Analysisof the T cell response in DC-treated mice suggested a general shift towards a Th2-dominated response, as determined by cytokine production following either concanavalin A or anti-TCR stimulation. Furthermore, sorted CD45RB(lo) CD25+ CD4+ T cells from the spleen of DC-treated mice produced high amounts of Th2 cytokines following anti-TCR stimulation, suggesting that these cells are responsible for the apparent Th2 shift. We conclude that DC therapy may have corrected the immunoregulatory defect in the NOD mouse, thus restoring a balance between pathogenic Th1 cells and protective Th2 cells.
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Maryam
M
Feili-Hariri
Dewayne H
DH
Falkner
Penelope A
PA
Morel
D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D016219:Immunotherapy, Adoptive / Q000379:methods; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology* / Q000473:pathology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D015375:Receptors, Interleukin-2 / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D015415:Biomarkers; D016207:Cytokines; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1