Gamma Delta T Cells in Shrimp Allergy Express a Unique Cytotoxic Cytokine Profile

Shellfish allergy is the most common food allergy in adults and the third most common in children. γδ T cells have been identified as playing a critical role in antigen tolerance in allergic diseases in mouse models. In humans, γδ T cells may play a regulatory role in peanut immunotherapy, and their role in shrimp allergy remains unclear. We hypothesized γδ T cells play a regulatory role in shrimp allergic disease. We performed single cell RNA sequencing (scRNAseq) on peripheral cells from shrimp allergic (SA) and healthy control (HC) subjects after stimulation with shrimp tropomyosin. This revealed a significant expansion of γδ T cells with three distinct clusters. One γδ T cell cluster predominated in SA, characterized as CD8+ with a cytotoxic expression profile. We found significant upregulation of TGF-β1 and downregulation of IL-7R in SA-stimulated γδ T cells, and IL-10RA expression in stimulated SA total PBMCs. γδ T cells may play a role in shrimp allergic disease through lymphocyte-mediated cytotoxin signaling and cytokine-mediated signaling pathways, including TGFβ-1, IL7/TSLP-IL7R, and IL10-IL10R pathways.