Eosinophilic Gastrointestinal Disease and Peanut Allergy are Alternatively Associated With IL-5+ and IL-5- Th2 Responses

Abstract

RATIONALE: Both anaphylactic food allergy and eosinophil associated gastrointestinal disorders (EGIDs) are associated with Th2 responses and food specific IgE, yet are clinically different. We determined if the clinical differences between these diseases are reflected in different Th2 responses to foods. METHODS: Peanut allergic (PA), allergic eosinophilic gastroenteritis (AEG) and nonatopic (NA) subjects were enrolled. Antigen specific IL-4, IL-5, IFN-γ and TNF T cell responses to peanut, soy and shrimp were measured using intracellular cytokine staining and polychromatic flow cytometry. RESULTS: Two distinct subpopulations of Th2 cells were found: IL-5+ Th2 (IL-4+, IL-5+) and IL-5- Th2 (IL-4+, IL-5-) cells. Peanut specific IL-5+ Th2 cells were present at a 20-fold greater frequency in AEG vs. PA (81 vs. 4 per 106 CD4 cells, p = 0.05), whereas similar frequencies of IL-5- Th2 cells were found (67 vs. 41 per 106). IL-5+ Th2 cells accounted for a significantly greater fraction of the food antigen specific cells in AEG relative to PA (29% vs. 4%, p < 0.0001). In PA, but not AEG, IL-5- Th2 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 Th1 responses to food Ags. CONCLUSION: Th2 responses are composed of two subpopulations: IL-5+ Th2 and IL-5- Th2 cells. IL-5+ Th2 food allergen specific T cells are singularly associated with AEG, whereas PA is associated with a dominant IL-5- Th2 response. These results suggest heterogeneity within the Th2 cytokine response, with different Th2 responses alternatively favoring IgE mediated or eosinophil dominant immunopathology.