Role of T Cell Sub-Populations in Food Allergy

Identification of immunological signatures for food allergic disease could enable objective assessment of disease severity and clinical manifestation for patient stratification. In this study we sought to assess heterogeneity of allergen-specific CD4+ T cell responses in food allergy. Ex-vivo pMHC-II tetramer staining enabled the direct comparison of Walnut-(n-17), Cashew-(n=11), Shrimp-(n=9), and Milk-(n=7) and Egg-(n=6)-specific CD4+ T-cell responses in allergic and non-allergic subjects. CD154+CD4+T-cell assay following short-term stimulation with antigenic-epitopes libraries were used for further functional analyses. The cooperation of CCR4+CCR6+ T-cells in allergic inflammation was assessed utilizing co-cultures of T-cell lines with neutrophils and B-cells. While different states of differentiation of allergen-specific TH2 cells can be observed between individuals, these cells were confined to food allergic subjects. Interestingly, a sub-population of TH17-like food allergen-specific cells that expressed gut-associated lymphoid tissue (CCR6+β7+) and secondary lymphoid organ homing markers (CCR7+) was also observed, suggesting a link with gastrointestinal clinical manifestation . The cytokine signatures of these T-cells confirmed TH2 and TH17-like profiles. Co-cultures of CCR4+CCR6+ T-cell lines generated neutrophil activation and IgE production by B-cells through the secretion of IL-4 indicating that this sub-population could play a role in food allergic symptoms. Highly heterogeneous T-cell responses were observed in food allergic subjects raising important questions of the pathophysiological role of each food allergen specific CD4+ T-cell subset in food allergy in general.