The natural killer T-cell ligand alpha-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice

Nat Med. 2001 Sep;7(9):1052-6. doi: 10.1038/nm0901-1052.


Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type 1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T cells. V alpha 14-J alpha 15 natural killer T (NKT) cells recognize lipid antigens presented by the major histocompatibility complex class I-like protein CD1d (refs. 3,4). We have previously shown that in vivo activation of V alpha 14 NKT cells by alpha-galactosylceramide (alpha-GalCer) and CD1d potentiates Th2-mediated adaptive immune responses. Here we show that alpha-GalCer prevents development of diabetes in wild-type but not CD1d-deficient NOD mice. Disease prevention correlated with the ability of alpha-GalCer to suppress interferon-gamma but not interleukin-4 production by NKT cells, to increase serum immunoglobulin E levels, and to promote the generation of islet autoantigen-specific Th2 cells. Because alpha-GalCer recognition by NKT cells is conserved among mice and humans, these findings indicate that alpha-GalCer might be useful for therapeutic intervention in human diseases characterized by Th1-mediated pathology such as Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1 / genetics
  • Autoantigens
  • Concanavalin A / pharmacology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Female
  • Galactosylceramides / pharmacology*
  • Glutamate Decarboxylase / immunology
  • Immunoglobulin E / blood
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Ligands
  • Mice
  • Mice, Inbred NOD
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Spleen / drug effects
  • Spleen / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / physiology


  • Antigens, CD1
  • Autoantigens
  • Galactosylceramides
  • Ligands
  • Concanavalin A
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma
  • Glutamate Decarboxylase