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

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. Here, we compare high dimensional phenotypes of innate and adaptive immune cell subsets of participants in a previously reported, 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) are associated with SU. Frequency of naïve CD8⁺ T cells shows a significant positive correlation with peanut-specific and Ara h 2-specific IgE levels at baseline. Higher frequencies of IL-4⁺ and IFNγ⁺ CD4⁺ T cells post-OIT are negatively correlated with SU. Our findings provide evidence that an immune signature consisting of certain CD8⁺ T cell subset frequencies is potentially predictive of SU following OIT.