Distinct trajectories distinguish antigen-specific T cells in peanut-allergic individuals undergoing oral immunotherapy

Background: Despite similar clinical symptoms, peanut-allergic (PA) individuals may respond quite differently to the same therapeutic interventions. Objective: This study aimed to determine whether inherent qualities of cell response at baseline could influence response to peanut oral immunotherapy (PnOIT). Methods: We first performed ex vivo T-cell profiling on peanut-reactive CD154⁺CD137⁺ T (pTeff) cells from 90 challenge-confirmed PA individuals. We developed a gating strategy for unbiased assessment of the phenotypic distribution of rare pTeff cells across different memory CD4⁺ T-cell subsets to define patient immunotype. In longitudinal samples of 29 PA participants enrolled onto the IMPACT trial of PnOIT, we determined whether patient immunotype at baseline could influence response to PnOIT. Results: Our data emphasize the heterogeneity of pTeff cell responses in PA participants with 2 mutually exclusive phenotypic entities (CCR6⁻CRT_H2⁺ and CCR6⁺CRT_H2⁻). Our findings lead us to propose that peanut allergy can be classified broadly into at least 2 discrete subtypes, termed immunotypes, with distinct immunologic and clinical characteristics that are based on the proportion of T_H2A pTeff cells. PnOIT induced elimination of T_H2A pTeff cells in the context of the IMPACT clinical trial. Only 1 PA patient with a low level of T_H2A pTeff cells at baseline experienced long-lasting benefit of remission after PnOIT discontinuation. Conclusion: Dividing PA patients according to their individual peanut-specific T-cell profile may facilitate patient stratification in clinical settings by identifying which immunotypes might respond best to different therapies.