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.