W106 - Evaluating Allergen-mediated MCT and MCTC Activation During Immunotherapy

Abstract Text: Mast cells (MCs) can be categorized into two distinct populations: subepithelial MCs that co-express tryptase and chymase (MCTC) and epithelial MCs that express tryptase alone (MCT). MCT are the principal phenotype found in airway epithelium, suggesting they are central drivers of aeroallergy. However, all current in-vitro systems give rise to MCTC. MC subsets are transcriptionally distinct from each other and differentially express key genes associated with IgG-driven inhibition, suggesting differential sensitivity to allergen-mediated desensitization. To test this, we selectively differentiated MCT and MCTC from peripheral blood-derived CD34+ cells, sensitized them using patient serum samples, and evaluated: 1) if differences in activation exist between MC subsets, and 2) whether immunotherapy improves MC subset activation. For this study, we utilized serum samples from a recent study of cat allergic individuals evaluating effects of subcutaneous immunotherapy (SCIT) on patient responses to cat dander. Our initial studies indicate that in-vitro differentiated MCT exhibit a 2-fold increase in degranulation compared with MCTC following activation with cat dander antigen. This enhanced MCT activation is especially pronounced when sensitized with serum from patients with low cat-specific IgE titers. Sensitizing MC subsets with SCIT treated patient serum samples improved MCT activation significantly more than MCTC activation, suggesting that MC subsets may exhibit differential sensitivity to activation during desensitization.