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.