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

Abstract

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.

SUSD2‐IL‐2 receptor interaction hinders antitumoral CD8+ T‐cell activity: Implications for cancer immunotherapy

“…Although this work addresses its role in cancer, SUSD2 may also regulate immune responses in allergic reactions. In fact, we believe that further research could be conducted in this context because CD8 + T cells were demonstrated to enhance allergic responses through the interaction with T helper type 2 cells 6 . In addition, SUSD2 was shown to be transcriptionally downregulated in atopic dermatitis skin lesions, 7 which could potentially promote allergen‐specific CD8 + T‐cell responses by removing SUSD2‐dependent T‐cell inhibitory regulation.…”

“…In fact, we believe that further research could be conducted in this context because CD8 + T cells were demonstrated to enhance allergic responses through the interaction with T helper type 2 cells. 6 In addition, SUSD2 was shown to be transcriptionally downregulated in atopic dermatitis skin lesions, 7 which could potentially promote allergen-specific CD8 + T-cell responses by removing SUSD2-dependent T-cell inhibitory regulation. Interestingly, surface SUSD2 expression has been recently detected in lung mast cells 8 correlating with their size and granularity, which might relate to an increased activation.…”

Low-dose oral immunotherapy in immunoglobulin E-mediated food allergies

“…The potential mechanisms behind this cell reduction remain unclear, although deletion, anergy, and exhaustion may all contribute ( 44 ). There was a notable decrease in the frequencies of IL-4 + , IL-9 + , and IL-10 + peanut-reactive CD4 + T cells among total CD4 + T cells in peanut-allergic individuals following OIT ( 47 ). Additionally, it was discovered that, compared with desensitization, higher frequencies of both IL-4 + CD4 + T cells and IFN-γ + CD4 + T cells post-OIT displayed a significant negative correlation with sustained unresponsiveness ( 47 ).…”

“…There was a notable decrease in the frequencies of IL-4 + , IL-9 + , and IL-10 + peanut-reactive CD4 + T cells among total CD4 + T cells in peanut-allergic individuals following OIT ( 47 ). Additionally, it was discovered that, compared with desensitization, higher frequencies of both IL-4 + CD4 + T cells and IFN-γ + CD4 + T cells post-OIT displayed a significant negative correlation with sustained unresponsiveness ( 47 ). Meanwhile, there was a significant reduction in the Th2-polarization surrogate marker OX40 expression in CD4 + T cells in peanut-allergic individuals after desensitization ( 47 ).…”

“…Th2 inflammatory cytokines, which mediate food allergies, are reduced by OIT, notably IL-5, IL-4, and IL-13. Peanut OIT significantly diminished type 2 cytokines IL-4, IL-5, IL-9, and IL-13 at week 104 in supernatants of peanut-stimulated peripheral blood mononuclear cells (PBMCs) ( 47 ). Meanwhile, Katharina Blumchen et al.…”