Expansion of the CD4 + effector T-cell repertoire characterizes peanut-allergic patients with heightened clinical sensitivity

J Allergy Clin Immunol. 2020 Jan;145(1):270-282. doi: 10.1016/j.jaci.2019.09.033. Epub 2019 Oct 22.

Abstract

Background: Individuals with peanut allergy range in clinical sensitivity: some can consume grams of peanut before experiencing any symptoms, whereas others suffer systemic reactions to 10 mg or less. Current diagnostic testing only partially predicts this clinical heterogeneity.

Objective: We sought to identify characteristics of the peanut-specific CD4+ T-cell response in peanut-allergic patients that correlate with high clinical sensitivity.

Methods: We studied the T-cell receptor β-chain (TCRβ) usage and phenotypes of peanut-activated, CD154+ CD4+ memory T cells using fluorescence-activated cell sorting, TCRβ sequencing, and RNA-Seq, in reactive and hyporeactive patients who were stratified by clinical sensitivity.

Results: TCRβ analysis of the CD154+ and CD154- fractions revealed more than 6000 complementarity determining region 3 sequences and motifs that were significantly enriched in the activated cells and 17% of the sequences were shared between peanut-allergic individuals, suggesting strong convergent selection of peanut-specific clones. These clones were more numerous among the reactive patients, and this expansion was identified within effector, but not regulatory T-cell populations. The transcriptional profile of CD154+ T cells in the reactive group skewed toward a polarized TH2 effector phenotype, and expression of TH2 cytokines strongly correlated with peanut-specific IgE levels. There were, however, also non-TH2-related differences in phenotype. Furthermore, the ratio of peanut-specific clones in the effector versus regulatory T-cell compartment, which distinguished the clinical groups, was independent of specific IgE concentration.

Conclusions: Expansion of the peanut-specific effector T-cell repertoire is correlated with clinical sensitivity, and this observation may be useful to inform our assessment of disease phenotype and to monitor disease longitudinally.

Keywords: CD154; CD4(+) T cell; Peanut allergy; RNA-Seq; T(H)2; TCRβ sequencing; clinical sensitivity; effector T cell; food allergy; regulatory T cell.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokines / immunology*
  • Female
  • Humans
  • Immunologic Memory*
  • Male
  • Peanut Hypersensitivity / immunology*
  • Peanut Hypersensitivity / pathology
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Th2 Cells / immunology*
  • Th2 Cells / pathology

Substances

  • Cytokines
  • Receptors, Antigen, T-Cell, alpha-beta