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J Allergy Clin Immunol. 2018 Jun;141(6):2107-2120. doi: 10.1016/j.jaci.2017.11.060. Epub 2018 Jan 31.

Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets.

Author information

1
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
2
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
3
Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Ark.
4
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Md.
5
Department of Pediatrics, University of North Carolina, Chapel Hill, NC.
6
Department of Pediatrics, National Jewish Health, Denver, Colo.
7
EMMES Corporation, Rockville, Md.
8
National Institutes of Health (National Institute of Allergy and Infectious Diseases), Bethesda, Md.
9
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
10
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: bojan.losic@mssm.edu.
11
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: cecilia.berin@mssm.edu.

Abstract

BACKGROUND:

The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood.

OBJECTIVES:

Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of subjects with and without peanut allergy (PA).

METHODS:

We obtained samples from patients with PA, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (Consortium of Food Allergy Research [CoFAR] 6). Subjects were confirmed as having PA, or if they passed a 1-g peanut challenge, they were termed high-threshold subjects. Healthy control (HC) subjects were also recruited. Peanut-responsive T cells were identified based on CD154 expression after 6 to 18 hours of stimulation with peanut extract. Cells were analyzed by using flow cytometry and single-cell RNA sequencing.

RESULTS:

Patients with PA had tissue- and follicle-homing peanut-responsive CD4+ T cells with a heterogeneous pattern of TH2 differentiation, whereas control subjects had undetectable T-cell responses to peanut. The PA group had a delayed and IL-2-dependent upregulation of CD154 on cells expressing regulatory T (Treg) cell markers, which was absent in HC or high-threshold subjects. Depletion of Treg cells enhanced cytokine production in HC subjects and patients with PA in vitro, but cytokines associated with highly differentiated TH2 cells were more resistant to Treg cell suppression in patients with PA. Analysis of gene expression by means of single-cell RNA sequencing identified T cells with highly correlated expression of IL4, IL5, IL9, IL13, and the IL-25 receptor IL17RB.

CONCLUSIONS:

These results demonstrate the presence of highly differentiated TH2 cells producing TH2-associated cytokines with functions beyond IgE class-switching in patients with PA. A multifunctional TH2 response was more evident than a Treg cell deficit among peanut-responsive T cells.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01904604.

KEYWORDS:

Food allergy; T(H)2; peanut allergy; regulatory T; tolerance

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