Transcriptional changes in peanut-specific CD4+ T cells over the course of oral immunotherapy.
Administration, Oral
Adolescent
Adult
Allergens
/ immunology
Arachis
/ immunology
CD4-Positive T-Lymphocytes
/ immunology
Child
Desensitization, Immunologic
Double-Blind Method
Female
Humans
Male
Middle Aged
Peanut Hypersensitivity
/ genetics
RNA-Seq
Transcription, Genetic
Transforming Growth Factor beta1
/ genetics
Young Adult
CD4+ T cell
Food allergy
OIT
Peanut allergy
RNAseq
Single cell
Journal
Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
06
03
2020
revised:
05
08
2020
accepted:
06
08
2020
pubmed:
14
8
2020
medline:
18
5
2021
entrez:
14
8
2020
Statut:
ppublish
Résumé
Oral immunotherapy (OIT) can successfully desensitize allergic individuals to offending foods such as peanut. Our recent clinical trial (NCT02103270) of peanut OIT allowed us to monitor peanut-specific CD4+ T cells, using MHC-peptide Dextramers, over the course of OIT. We used a single-cell targeted RNAseq assay to analyze these cells at 0, 12, 24, 52, and 104 weeks of OIT. We found a transient increase in TGFβ-producing cells at 52 weeks in those with successful desensitization, which lasted until 117 weeks. We also performed clustering and identified 5 major clusters of Dextramer+ cells, which we tracked over time. One of these clusters appeared to be anergic, while another was consistent with recently described TFH13 cells. The other 3 clusters appeared to be Th2 cells by their coordinated production of IL-4 and IL-13, but they varied in their expression of STAT signaling proteins and other markers. A cluster with high expression of STAT family members also showed a possible transient increase at week 24 in those with successful desensitization. Single cell TCRαβ repertoire sequences were too diverse to track clones over time. Together with increased TGFβ production, these changes may be mechanistic predictors of successful OIT that should be further investigated.
Identifiants
pubmed: 32783912
pii: S1521-6616(20)30728-2
doi: 10.1016/j.clim.2020.108568
pmc: PMC7484319
mid: NIHMS1619058
pii:
doi:
Substances chimiques
Allergens
0
TGFB1 protein, human
0
Transforming Growth Factor beta1
0
Banques de données
ClinicalTrials.gov
['NCT02103270']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
108568Subventions
Organisme : NIAID NIH HHS
ID : R01 AI125567
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI104209
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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