iNKT cells contribute to the allergic response in mice orally sensitised for cow's milk protein

Background: Little is known about the contribution of the invariant natural killer T (iNKT)-cells in the onset of food allergy. Using a mouse model for cow's milk allergy the function of iNKT cells was investigated. α-Galactosylceramide (αGalCer), a specific iNKT cell agonist, was used to stimulate iNKT cells. Methods: Female C3H/HeOuJ mice were sensitized five times orally with caseins or whey proteins. One hour before the sensitizations mice were treated intraperitoneally with αGalCer (2 μg/mice) or control. One week after the last sensitization mice were challenged intradermally in the ear and acute allergic skin reaction was measured. Sera were analyzed for specific immunoglobulins. In the liver, spleen and mesenteric lymph nodes (MLN) percentages of iNKT cells were analyzed and liver lymphocyte restimulation assays were performed. Results: The percentage of iNKT cells in the liver of casein- and whey-sensitized mice was reduced when compared to sham-sensitized mice, while it was enhanced in the spleen and MLN of whey-sensitized mice. Mice treated with αGalCer showed enhanced acute allergic skin reactions in comparison with sham treated casein (P <0.05) or whey (P <0.001) sensitized mice. This finding was associated with increased levels of whey- but not casein-specific immunoglobulins. αGalCer treatment was found to deplete iNKT cells in the liver of sensitized as well as shamsensitized mice, and these hepatocytes did not respond to ex vivo restimulation with αGalCer. αGalCer treatment abrogated the increase in iNKT% in the spleen upon whey-sensitization. Conclusion: Hepatocytes were functionally depleted for iNKT cells upon αGalCer treatment. This was associated with an increased allergic effector response and enhanced whey-specific immunoglobulin levels. In conclusion, iNKT cells may suppress cow's milk allergic symptoms in mice orally sensitized for whey or casein.