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

Abhinav Kaushik, Diane Dunham, Xiaorui Han, Evan Do, Sandra Andorf, Sheena Gupta, Andrea Fernandes, Laurie Elizabeth Kost, Sayantani B. Sindher, Wong Yu, Mindy Tsai, Robert Tibshirani, Scott D. Boyd, Manisha Desai, Holden T. Maecker, Stephen J. Galli, R. Sharon Chinthrajah, Rosemarie H. DeKruyff, Monali Manohar and Kari C. Nadeau ()
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Abhinav Kaushik: Stanford University School of Medicine
Diane Dunham: Stanford University School of Medicine
Xiaorui Han: Stanford University School of Medicine
Evan Do: Stanford University School of Medicine
Sandra Andorf: Stanford University School of Medicine
Sheena Gupta: Stanford University School of Medicine
Andrea Fernandes: Stanford University School of Medicine
Laurie Elizabeth Kost: Stanford University School of Medicine
Sayantani B. Sindher: Stanford University School of Medicine
Wong Yu: Stanford University School of Medicine
Mindy Tsai: Stanford University School of Medicine
Robert Tibshirani: Stanford University
Scott D. Boyd: Stanford University School of Medicine
Manisha Desai: Stanford University
Holden T. Maecker: Stanford University School of Medicine
Stephen J. Galli: Stanford University School of Medicine
R. Sharon Chinthrajah: Stanford University School of Medicine
Rosemarie H. DeKruyff: Stanford University School of Medicine
Monali Manohar: Stanford University School of Medicine
Kari C. Nadeau: Stanford University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34222-8

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