Gamma Delta T Cells Mediate Shrimp Allergy Through Regulatory Cytokine Pathways

Shrimp allergy is the second most common food allergy in the United States. ?d T cells play a regulatory role in peanut immunotherapy, but their role in shrimp allergy remains unclear. We hypothesized ?d T cells play a regulatory role in shrimp allergic disease. We performed single cell RNA sequencing on peripheral cells from shrimp allergic (SA) and healthy control (HC) subjects after stimulation with shrimp tropomyosin. We found significant expansion of ?d T cells and three distinct clusters. One ?d T cell cluster predominated in SA, characterized as CD8+ with a cytotoxic expression profile. We found significant upregulation of TGF-ß1 and downregulation of IL-7R in SA-stimulated vs. HC-stimulated ?d T cells, and IL-10 secretion in stimulated SA ?d T cells. ?d T cells play an important role in the pathogenesis of shrimp allergy through lymphocyte-mediated cytotoxin signaling and cytokine-mediated signaling pathways, including TGFß-1, IL7/TSLP-IL7R, and IL10-IL10R pathways. Overall design: Single-cell RNA sequencing of unstimulated (tropomyosin: 0 ug/mL) and stimulated (tropomyosin: 1 ug/mL) healthy and shrimp allergic patients