Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells
Name
150634.2-20220114171205-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Description
Published version
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8.43 MB
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Checksum (MD5)
8eea6e5bc1c5cee535539a414f3ab2d3
Author(s)
Monian, Brinda
Tu, Ang A
Ruiter, Bert
Morgan, Duncan M
Petrossian, Patrick M
Smith, Neal P
Gierahn, Todd M
Ginder, Julia H
Shreffler, Wayne G
Love, J Christopher
Date Issued
November 23, 2021
Journal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Citation
Monian, Brinda, Tu, Ang A, Ruiter, Bert, Morgan, Duncan M, Petrossian, Patrick M et al. 2021. "Peanut oral immunotherapy differentially suppresses clonally distinct subsets of T helper cells." Journal of Clinical Investigation, 132 (2).
Version
Final published version
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/β (TCRα/β) 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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Broad Institute of MIT and Harvard
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DOI of Published Version
https://doi.org/10.1172/JCI150634
