Lj. Saubermann et al., Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice, GASTROENTY, 119(1), 2000, pp. 119
Background & Aims: CD1d is a major histocompatibility complex class I-like
molecule that presents glycolipid antigens to a subset of natural killer (N
K)1.1(+) T cells. These NK T cells exhibit important immunoregulatory funct
ions in several autoimmune disease models. Methods: To investigate whether
CD1d and NK T cells have a similar role in intestinal inflammation, the eff
ects 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-Gal
Cer 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, bleedi
ng, 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 o
f NK T cells preactivated by alpha-GalCer, but not alpha-ManCer, resulted i
n diminished colitis. Using a fluorescent-labeled analogue of alpha-GalCer,
confocal microscopy localized alpha-GalCer to the colonic surface epitheli
um of WT but not CD1d(-/-) mice, indicating alpha-GalCer binds CD1d in the
intestinal epithelium and may be functionally active at this site. Conclusi
ons: These results show an important functional role for NK T cells, activa
ted by alpha-GalCer in a CD1d-restricted manner, in regulating intestinal i
nflammation.