Dual assessment of peanut-specific effector and regulatory T cells in patients undergoing oral immunotherapy
Monday, March 6, 2017
Exhibit Hall B2 (Georgia World Congress Center, Building B)
Blake J. Rust, Veronique Bajzik, Brian P. Vickery, MD FAAAAI, Erik R. Wambre, PhD, MBE
Rationale:  The clinical application of food immunotherapy would greatly benefit from the development of reliable immune monitoring assays that could address the complexity and functional heterogeneity of food allergy. Antigen-specific assays for effector T cells are well characterized, however similar assays for regulatory T cells are still lacking.

Methods: Coded samples (n=50) to the operator were provided during a randomized, double-blinded, placebo-controlled trial (ARC003) of characterized oral desensitization immunotherapy (CODIT) in peanut-allergic patients. Eligible subjects reacted to ≤ 100 mg peanut protein during a screening double-blind placebo-controlled food challenge (DBPCFC).The magnitude and quality of baseline peanut-specific T-cell responses were determined ex vivousing both CD154 and CD137 upregulation assay.

Results:  Highly heterogeneous effector CD4+ T cell responses were observed in peanut-allergic subjects, raising important questions regarding the pathophysiological role of each allergen specific CD4+T-cell subset in food allergy. In subjects reacting to DBPCFC, we observed two distinct phenotypes in the effector CD4+ memory populations, a classical allergic TH2A phenotype (CD27- CRTH2+ CCR4+ CCR6-) and a Th17-like phenotype (CD27- CRTH2- CCR4+ CCR6+). Conversely, non-reactive subjects had low frequency of peanut-reactive T cells with a profile similar to non-allergic individuals (CD27+ CRTH2- CCR4- CCR6+). Interestingly, for each group we observed low frequencies of antigen-specific regulatory T cells that have an extremely stable phenotype (CD27+ Helios+ CTLA-4+ Foxp3+). 

Conclusions: Heterogeneity of baseline peanut-specific effector T cell responses suggests that cellular phenotypes may associate with or predict clinical treatment outcomes following CODIT in subjects with peanut allergy.