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Reversal of established autoimmune diabetes by H60‐loaded immature dendritic cells plus the natural killer T cells ligand alpha‐Galactosylceramide
Author(s) -
Yang Wen,
Song Xiaoping,
Chung Kyungmee,
Wilson Brian
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1074.29
Subject(s) - nod mice , nod , cd1d , immunology , dendritic cell , major histocompatibility complex , natural killer t cell , immune system , biology , endocrinology , t cell , diabetes mellitus
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 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 64% of cyclophosphamide (CY)‐induced diabetic NOD mice. Reversal of diabetes requires both iNKT‐based therapy and CD1d expression by the infused DC because only 10% of recovery of glycemic control was noted when CD1d(−/−)‐DC where infused or iNKT activation was not included. To investigate the resource of islets regeneration, we use RIP‐CreER; Z/AP bi‐transgenic NOD mice. We find that most insulin positive cells express HPAP in the islets of non‐diabetic bi‐transgenic NOD mice, but very few insulin positive cells express HPAP in the islets of reversed bi‐transgenic NOD mice. 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, and islets regeneration may be mainly the result of differentiation of pancreatic progenitor cells.