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.