Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice

Gastroenterology. 2000 Jul;119(1):119-28. doi: 10.1053/gast.2000.9114.


Background & aims: CD1d is a major histocompatibility complex class I-like molecule that presents glycolipid antigens to a subset of natural killer (NK)1.1(+) T cells. These NK T cells exhibit important immunoregulatory functions in several autoimmune disease models.

Methods: To investigate whether CD1d and NK T cells have a similar role in intestinal inflammation, the effects of the glycolipid, alpha-galactosylceramide (alpha-GalCer), on dextran sodium sulfate (DSS)-induced colitis were examined. Wild-type (WT), CD1d(-/-), and RAG(-/-) mice were examined for their response to either alpha-GalCer or the control analogue, alpha-mannosylceramide (alpha-ManCer).

Results: WT mice, but not CD1d(-/-) and RAG(-/-) mice, receiving alpha-GalCer had a significant improvement in DSS-induced colitis based on body weight, bleeding, diarrhea, and survival when compared with those receiving alpha-ManCer. Elimination of NK T cells through antibody-mediated depletion resulted in a reduction of the effect of alpha-GalCer. Furthermore, adoptive transfer of NK T cells preactivated by alpha-GalCer, but not alpha-ManCer, resulted in diminished colitis. Using a fluorescent-labeled analogue of alpha-GalCer, confocal microscopy localized alpha-GalCer to the colonic surface epithelium of WT but not CD1d(-/-) mice, indicating alpha-GalCer binds CD1d in the intestinal epithelium and may be functionally active at this site.

Conclusions: These results show an important functional role for NK T cells, activated by alpha-GalCer in a CD1d-restricted manner, in regulating intestinal inflammation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD1 / genetics
  • Antigens, CD1 / pharmacology*
  • Antigens, CD1d
  • Colitis / chemically induced
  • Colitis / prevention & control*
  • Dextran Sulfate
  • Galactosylceramides / pharmacokinetics
  • Galactosylceramides / pharmacology*
  • Genes, RAG-1 / genetics
  • Intestinal Mucosa / metabolism
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout / genetics
  • Protein Isoforms / pharmacokinetics
  • Protein Isoforms / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology*


  • Antigens, CD1
  • Antigens, CD1d
  • Galactosylceramides
  • Protein Isoforms
  • Dextran Sulfate