The aim of this study was to determine the effect of beta-
glycosphingolipids on intra-hepatic natural killer T (NKT) lymphocyte regulatory function and on lymphocyte trapping via alteration of
cell membrane lipid rafts. Immune-mediated
colitis was induced by intracolonic instillation of trinitrobenzene
sulfonic acid. Mice were treated with beta-
lactosylceramide (LC), beta-
glucosylceramide (GC), beta-
galactosylceramide,
ceramide, or a combination of both GC and LC (IGL), or
solvent alone.
Lipid rafts were investigated by fluorescence-activated cell sorting analysis of ganglioside-GM1 and fluorescence microscopy of structure. Administration of beta-
glycosphingolipids resulted in an increased intrahepatic/peripheral NKT ratio, increased intrahepatic CD8+ lymphocyte trapping, decreased serum
interferon-gamma (IFN-gamma) levels and decreased serum IFN-gamma/
interleukin-10 ratio. Administration of GC, LC, or IGL significantly altered the levels of GM1, a key marker of
lipid rafts, on NKT regulatory lymphocytes. The immune modulatory effect of beta-
glycosphingolipids was associated with increased survival and significant alleviation of
colitis as determined by improvement in both the macroscopic and microscopic scores. In conclusion, administration of beta-
glycosphingolipids increased NKT regulatory lymphocyte redistribution and intrahepatic CD8(+) T lymphocyte trapping, resulting in alleviation of immune-mediated
colitis. The effects of these naturally occurring compounds were associated with modification of the T lymphocyte
lipid raft structure, which is a site for immune modulation.