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- Title
Reversal of Established Autoimmune Diabetes by H60-Loaded Immature Dendritic Cells Plus the Natural Killer T Cells Ligand α-Galactosylceramide.
- Authors
Yang, Wen; Chung, Kyungmee; Song, Xiaoping; Wilson, Brian
- Abstract
Activation of iNKT cells controls the development of tolerogenic dendritic cells in NOD mice. Here we show that the combination of iNKT cell activation and transfer of antigen-loaded DC can reverse diabetes in the NOD mouse model. To examine whether class I restricted antigens derived from innate immume receptors can be used with DC, an immunodominant H60 minor histocompatibility (H) antigen-derived peptide presented by H-2K[sup b] MHC class I was loaded into bone marrow-derived DC and used to treat diabetic NOD mice. Notably, concurrent treatment of NOD mice with H60-loaded DC and the iNKT superagonist α-GalCer resulted in long-term remission of ∼70% of cyclophosphamide (CY)-induced diabetic NOD mice. Reversal of diabetes requires both iNKT-based therapy and CD1d expression by the infused DC because no recovery of glycemic control was noted when CD1d(-/-)-DC where infused or iNKT activation was not included. Hence, self-tolerance and subsequent β-cell function can be restored in overtly diabetic mice via the modulation of antigen-loaded DC and iNKT cells.
- Subjects
DIABETES; AUTOIMMUNE diseases; ANTIGENS; DENDRITIC cells; KILLER cells; T cells; CEREBROSIDES; MICE
- Publication
Diabetes, 2007, Vol 56, pA60
- ISSN
0012-1797
- Publication type
Article