Activation of natural killer T cells by α-galactosylceramide treatment prevents the onset and recurr
Author: ["Shayan Sharif","Guillermo A. Arreaza","Peter Zucker","Qing-Sheng Mi","Jitin Sondhi","Olga V. Naidenko","Mitchell Kronenberg","Yasuhiko Koezuka","Terry L. Delovitch","Jean-Marc Gombert","Maria Leite-de-Moraes","Christine Gouarin","Ren Zhu","Agathe Hameg","Toshinori Nakayama","Masaru Taniguchi","Françoise Lepault","Agnès Lehuen","Jean-François Bach","André Herbelin"]
Publication: Nature Medicine
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Abstract
Type 1 diabetes (T1D) in non-obese diabetic (NOD) mice may be favored by immune dysregulation leading to the hyporesponsiveness of regulatory T cells and activation of effector T-helper type 1 (Th1) cells1. The immunoregulatory activity of natural killer T (NKT) cells is well documented2,3, and both interleukin (IL)-4 and IL-10 secreted by NKT cells have important roles in mediating this activity4,5. NKT cells are less frequent and display deficient IL-4 responses in both NOD mice6,7 and individuals at risk for T1D (ref. 8), and this deficiency may lead to T1D (refs. 1,6–9). Thus, given that NKT cells respond to the α-galactosylceramide (α-GalCer) glycolipid in a CD1d-restricted manner by secretion of Th2 cytokines10,11,12, we reasoned that activation of NKT cells by α-GalCer might prevent the onset and/or recurrence of T1D. Here we show that α-GalCer treatment, even when initiated after the onset of insulitis, protects female NOD mice from T1D and prolongs the survival of pancreatic islets transplanted into newly diabetic NOD mice. In addition, when administered after the onset of insulitis, α-GalCer and IL-7 displayed synergistic effects, possibly via the ability of IL-7 to render NKT cells fully responsive to α-GalCer. Protection from T1D by α-GalCer was associated with the suppression of both T- and B-cell autoimmunity to islet β cells and with a polarized Th2-like response in spleen and pancreas of these mice. These findings raise the possibility thatα-GalCer treatment might be used therapeutically to prevent the onset and recurrence of human T1D.
Cite this article
Sharif, S., Arreaza, G., Zucker, P. et al. Activation of natural killer T cells by α-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes. Nat Med 7, 1057–1062 (2001). https://doi.org/10.1038/nm0901-1057
