Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin.

Background A key immunologic feature of food allergy (FA) is the presence of a T h 2-type cytokine bias. Ligation of the invariant natural killer T cell (iNKT) T-cell receptor (TCR) by sphingolipids presented via the CD1d molecule leads to copious secretion of T h 2-type cytokines. Major food allergens (eg, milk, egg) are the richest dietary source of sphingolipids (food-derived sphingolipids [food-SLs]). Nonetheless, the role of iNKTs in FA is unknown. Objective To investigate the role of iNKTs in FA and to assess whether food-SL–CD1d complexes can engage the iNKT-TCR and induce iNKT functions. Methods PBMCs from 15 children with cow's milk allergy (MA), 12 children tolerant to cow's milk but with allergy to egg, and 13 healthy controls were incubated with α-galactosylceramide (αGal), cow's milk–sphingomyelin, or hen's egg–ceramide. iNKTs were quantified, and their cytokine production and proliferation were assessed. Human CD1d tetramers loaded with milk-sphingomyelin or egg-ceramide were used to determine food-SL binding to the iNKT-TCR. Results Milk-sphingomyelin, but not egg-ceramide, can engage the iNKT-TCR and induce iNKT proliferation and T h 2-type cytokine secretion. Children with FA, especially those with MA, had significantly fewer peripheral blood iNKTs and their iNKTs exhibited a greater T h 2 response to αGal and milk-sphingomyelin than iNKTs of healthy controls. Conclusion iNKTs from children with FA, especially those with MA, are reduced in number and exhibit a T h 2 bias in response to αGal and milk-sphingomyelin. These data suggest a potential role for iNKTs in FA.