Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells.
J Clin Invest
; 132(2)2022 01 18.
Article
in En
| MEDLINE
| ID: mdl-34813505
ABSTRACT
Food allergy affects an estimated 8% of children in the United States. Oral immunotherapy (OIT) is a recently approved treatment, with outcomes ranging from sustained tolerance to food allergens to no apparent benefit. The immunological underpinnings that influence clinical outcomes of OIT remain largely unresolved. Using single-cell RNA-Seq and paired T cell receptor α/ß (TCRα/ß) sequencing, we assessed the transcriptomes of CD154+ and CD137+ peanut-reactive T helper (Th) cells from 12 patients with peanut allergy longitudinally throughout OIT. We observed expanded populations of cells expressing Th1, Th2, and Th17 signatures that further separated into 6 clonally distinct subsets. Four of these subsets demonstrated a convergence of TCR sequences, suggesting antigen-driven T cell fates. Over the course of OIT, we observed suppression of Th2 and Th1 gene signatures in effector clonotypes but not T follicular helper-like (Tfh-like) clonotypes. Positive outcomes were associated with stronger suppression of Th2 signatures in Th2A-like cells, while treatment failure was associated with the expression of baseline inflammatory gene signatures that were present in Th1 and Th17 cell populations and unmodulated by OIT. These results demonstrate that differential clinical responses to OIT are associated with both preexisting characteristics of peanut-reactive CD4+ T cells and suppression of a subset of Th2 cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arachis
/
Desensitization, Immunologic
/
Receptors, Antigen, T-Cell, alpha-beta
/
T-Lymphocytes, Helper-Inducer
/
Peanut Hypersensitivity
/
Single-Cell Analysis
/
RNA-Seq
Type of study:
Clinical_trials
Limits:
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Clin Invest
Year:
2022
Document type:
Article