title: Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors: Soma
authors: S
authors: Jyonouchi
authors: Valsamma
authors: V
authors: Abraham
authors: Jordan S
authors: JS
authors: Orange
authors: Jonathan M
authors: JM
authors: Spergel
authors: Laura
authors: L
authors: Gober
authors: Emily
authors: E
authors: Dudek
authors: Rushani
authors: R
authors: Saltzman
authors: Kim E
authors: KE
authors: Nichols
authors: Antonella
authors: A
authors: Cianferoni
mesh_terms: D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D016269:Milk Hypersensitivity / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013109:Sphingomyelins / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D013109:Sphingomyelins