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-γ, 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 – 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.