Th100 - Cashew and Shrimp Oral Immunotherapy-induced Changes in Allergen-reactive CD4+ T Cells

Abstract Text: Among food-allergic events, nuts like cashew and shellfish such as shrimp, are often implicated in anaphylaxis. Here we look at immunological responses with oral immunotherapy (OIT) treatment, specifically changes in allergen-specific T cells. We studied 52 participants with allergies to either cashew (40) or shrimp (12) from an open-label, Phase 2 clinical trial- MOTIF(NCT03504774). 52 weeks of OIT was followed by 6 weeks of avoidance and oral food challenges were performed at baseline, post-OIT (Week 52) and post-avoidance (Week 58). Participants were assessed for their ability to achieve allergen desensitization and sustained unresponsiveness. Multicolor flow cytometry identified allergen-reactive (CD69+CD40L+) CD4+ T cells post specific allergen stimulation at all three timepoints. At week 52 and week 58, there was a significant decrease in cashew-reactive pathogenic Th2 CD4+CRTH2+ cells from baseline (p = 0.0485). We also used cashew- and shrimp-epitope specific tetramers to immunophenotype specific CD4+ T cells among unstimulated PBMCs from compatible participants to 5 HLA subtypes. The majority (> 85%) of tetramer+ CD4+ T cells exhibited memory (CD45RA-) phenotype with Th2-A polarization (CRTH2+ CXCR3- CXCR5-) at baseline. There was a significant decrease (p=0.0474) in frequency of tetramer+ CD4+ T cells with a baseline frequency of 0.77%, reducing to 0.41% and 0.22%, at weeks 52 and 58 respectively. We also observed a significant increase in the frequency of CCR6+ tetramer+ CD4+ T cells (p=0.0387) at weeks 52 and 58. These results could potentially enhance the prospect for better OIT for other allergens by providing insight into the immune mechanisms behind it.