Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5⁺ and IL-5⁻ T_H2 responses

Background

Both anaphylactic food allergy and eosinophil-associated gastrointestinal disorders are associated with T_H2 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_H2 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_H2 cells were found: IL-5⁺ T_H2 (IL-4⁺, IL-5⁺) and IL-5^– T_H2 (IL-4⁺, IL-5^–) cells. Peanut-specific IL-5⁺ T_H2 cells were present at a 20-fold greater frequency in AEG versus PA (81 vs 4 per 10⁶ CD4 cells; P = .05), whereas there were similar frequencies of IL-5^- T_H2 cells (67 vs 41 per 10⁶). For all foods, IL-5⁺ T_H2 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_H2 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_H1 responses to food antigens.

Conclusion

T_H2 responses are composed of 2 subpopulations: IL-5⁺ T_H2 and IL-5^– T_H2 cells. IL-5⁺ T_H2 food allergen–specific T cells are singularly associated with AEG, whereas PA is associated with a dominant IL-5^– T_H2 response. These results suggest heterogeneity within the T_H2 cytokine response, with different T_H2 responses alternatively favoring IgE-mediated or eosinophil-dominant immunopathology.

Key words: Food allergy, peanut, T cell, T_H2, eosinophil-associated gastrointestinal disease, IL-4, IL-5, flow cytometry

Abbreviations used: AEG, Allergic eosinophilic gastroenteritis, EG, Eosinophilic gastroenteritis, EGID, Eosinophil-associated gastrointestinal disorder, EoE, Eosinophilic esophagitis, NA-EG, Nonallergic eosinophilic gastroenteritis, NIAID, National Institute of Allergy and Infectious Diseases, PA, Peanut allergy