Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5+ and IL-5- TH2 responses

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,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 106). 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. Conclusion: 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. (J Allergy Clin Immunol 2009;124:1326-32.)