title: Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5+ and IL-5(-) T(H)2 responses.
abstract: BACKGROUND
  Both anaphylactic food allergy and eosinophil-associated gastrointestinal disorders are associated with T(H)2 responses and food-specific IgE, yet they have very different clinical presentations.
  
  
  OBJECTIVE
  To determine whether the clinical differences between anaphylactic food allergy and eosinophil-associated gastrointestinal disorders are reflected in different T(H)2 responses to foods.
  
  
  METHODS
  Subjects with peanut allergy (PA), subjects with allergic eosinophilic gastroenteritis (AEG), and nonatopic subjects were enrolled. Antigen-specific IL-4, IL-5, IFN-gamma, and TNF T-cell responses to peanut, soy, and shrimp were measured by using intracellular cytokine staining and polychromatic flow cytometry.
  
  
  RESULTS
  Two distinct subpopulations of T(H)2 cells were found: IL-5+ T(H)2 (IL-4+, IL-5+) and IL-5(-) T(H)2 (IL-4+, IL-5(-)) cells. Peanut-specific IL-5+ T(H)2 cells were present at a 20-fold greater frequency in AEG versus PA (81 vs 4 per 10(6) CD4 cells; P = .05), whereas there were similar frequencies of IL-5(-) T(H)2 cells (67 vs 41 per 10(6)). For all foods, IL-5+ T(H)2 cells accounted for a significantly greater fraction of the antigen-specific cells in AEG relative to PA (29% vs 4%; P < .0001). In PA but not AEG, IL-5(-) T(H)2 responses to peanut were highly correlated with peanut-specific IgE (r = 0.87 vs 0.55, respectively). All subject groups elicited similar very low-magnitude T(H)1 responses to food antigens.
  
  
  CONCLUSIONS
  T(H)2 responses are composed of 2 subpopulations: IL-5+ T(H)2 and IL-5(-) T(H)2 cells. IL-5+ T(H)2 food allergen-specific T cells are singularly associated with AEG, whereas PA is associated with a dominant IL-5(-) T(H)2 response. These results suggest heterogeneity within the T(H)2 cytokine response, with different T(H)2 responses alternatively favoring IgE-mediated or eosinophil-dominant immunopathology.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA. cprussin@niaid.nih.gov
authors.forename: Calman
authors.initials: C
authors.lastname: Prussin
authors.forename: Joohee
authors.initials: J
authors.lastname: Lee
authors.forename: Barbara
authors.initials: B
authors.lastname: Foster
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D010367:Arachis / Q000276:immunology; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005759:Gastroenteritis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D021183:Peanut Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D055815:Young Adult
chemical_list: D000485:Allergens; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma