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

• Published in: Nature communications Vol. 13; no. 1; pp. 6646 - 12
• Main Authors: Kaushik, Abhinav, Dunham, Diane, Han, Xiaorui, Do, Evan, Andorf, Sandra, Gupta, Sheena, Fernandes, Andrea, Kost, Laurie Elizabeth, Sindher, Sayantani B., Yu, Wong, Tsai, Mindy, Tibshirani, Robert, Boyd, Scott D., Desai, Manisha, Maecker, Holden T., Galli, Stephen J., Chinthrajah, R. Sharon, DeKruyff, Rosemarie H., Manohar, Monali, Nadeau, Kari C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/31; 631/250/1619/554/1834; 631/250/1619/554/1898/1274; 631/250/2152/1566/2493; 631/250/251; Administration, Oral; Allergens; Allergic reactions; Allergies; Ara h 2 antigen; Arachis; CD4 antigen; CD57 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Cell Differentiation; Clinical trials; Correlation; Desensitization; Desensitization, Immunologic - methods; Differentiation (biology); Feasibility Studies; Food; Food allergies; Humanities and Social Sciences; Immune system; Immunoglobulin E; Immunologic Factors; Immunotherapy; Interleukin 4; Lymphocytes; Lymphocytes T; multidisciplinary; Peanut Hypersensitivity - therapy; Peanuts; Phenotypes; Science; Science (multidisciplinary); γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34222-8

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. Oral immunotherapy (OIT) clinical trials have helped a subset of participants achieve sustained unresponsiveness (SU) to the cognate allergen. Here the authors analyse immune cells from participants from one peanut OIT trial and show that CD8 + T cell differentiation status at baseline may help to predict the likelihood of achieving SU.