CD8+ T cell differentiation status correlates with the feasibility of sustained unresponsiveness following oral immunotherapy

While food allergy oral immunotherapy (OIT) can provide safe and effective desensitization (DS), the immune mechanisms underlying development of sustained unresponsiveness (SU) following a period of avoidance are largely unknown. We compared high dimensional immunophenotypes of innate and adaptive immune cell subsets of participants in a phase 2 randomized, controlled, peanut OIT trial who achieved SU vs. DS (no vs. with allergic reactions upon food challenge after a withdrawal period; n=21 vs. 30 respectively among total 120 intent-to-treat participants). Lower frequencies of naïve CD8+ T cells and terminally differentiated CD57+ CD8+ T cell subsets at baseline (pre-OIT) were highly associated with SU. Frequency of naïve CD8+ T cells showed a significant positive correlation with peanut- and Ara h 2-specific IgE at baseline. Higher frequencies of IL-4+ and IFNg+ CD8+ T cells post-OIT were negatively correlated with SU. Our findings provide compelling evidence that an immune signature consisting of certain CD8+ T cell subset frequencies is predictive of SU following OIT.