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<p>Oral immunotherapy (OIT) is the only U.S. Food and Drud Administration-approved treatment for peanut allergy. Peanut-reactive (pr) CD4<sup>+</sup> T cells are pivotal in peanut allergy pathogenesis and OIT-induced desensitization. However, the underlying pr CD4<sup>+</sup> T cell immune mechanisms leading to sustained unresponsiveness after OIT discontinuation are largely unknown. We analyzed single-cell RNA and protein immunophenotypes and T cell receptor repertoires of pr CD4<sup>+</sup> T cells from a phase 2 peanut OIT trial cohort. We identified increased cytotoxicity-related phenotypes and type 1 helper cytotoxic T lymphocyte-like cell clonal expansion during OIT, while type 2 helper T (T<sub>H</sub>2) cell-related phenotypes and T<sub>H</sub>2-like cell clonal expansion decreased. OIT participants achieving sustained unresponsiveness were distinguished by lower baseline T<sub>H</sub>2-related phenotypes, elevated post-OIT cytotoxicity-related pr effector T cell gene signatures and higher CD39 expression in pr regulatory T cells. These findings clarify OIT-induced CD4<sup>+</sup> T cell tolerance mechanisms and can guide effective allergen-specific OIT strategies.</p>

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Peanut allergy oral immunotherapy drives single-cell multi-omic changes in peanut-reactive T cells associated with sustained unresponsiveness

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月4日

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  • Xiaorui Han,
  • Valeria Skatova,
  • Artem Mikelov,
  • Xuhuai Ji,
  • Ramona A. Hoh,
  • Ji-Yeun Lee,
  • Shu Cao,
  • Hana Seastedt,
  • Jackson Schuetz,
  • Andrea Fernandes,
  • Arpita Singhal,
  • Fabian Grubert,
  • Rosemarie H. DeKruyff,
  • Holden T. Maecker,
  • Stephen J. Galli,
  • Monali Manohar,
  • R. Sharon Chinthrajah,
  • Maya M. Kasowski,
  • Scott D. Boyd,
  • Kari C. Nadeau

摘要

Oral immunotherapy (OIT) is the only U.S. Food and Drud Administration-approved treatment for peanut allergy. Peanut-reactive (pr) CD4+ T cells are pivotal in peanut allergy pathogenesis and OIT-induced desensitization. However, the underlying pr CD4+ T cell immune mechanisms leading to sustained unresponsiveness after OIT discontinuation are largely unknown. We analyzed single-cell RNA and protein immunophenotypes and T cell receptor repertoires of pr CD4+ T cells from a phase 2 peanut OIT trial cohort. We identified increased cytotoxicity-related phenotypes and type 1 helper cytotoxic T lymphocyte-like cell clonal expansion during OIT, while type 2 helper T (TH2) cell-related phenotypes and TH2-like cell clonal expansion decreased. OIT participants achieving sustained unresponsiveness were distinguished by lower baseline TH2-related phenotypes, elevated post-OIT cytotoxicity-related pr effector T cell gene signatures and higher CD39 expression in pr regulatory T cells. These findings clarify OIT-induced CD4+ T cell tolerance mechanisms and can guide effective allergen-specific OIT strategies.