Modulation of CRTh2 expression on allergen-specific T cells following peptide immunotherapy

Allergy. 2019 Nov;74(11):2157-2166. doi: 10.1111/all.13867. Epub 2019 Jun 7.

Abstract

Background: Allergen immunotherapy using synthetic peptide T-cell epitopes (Cat-PAD) from the major cat allergen Fel d 1 has been shown, in allergen exposure studies, to significantly reduce symptoms of allergic rhinoconjunctivitis in cat-allergic subjects. However, the immunological mechanisms underlying clinical benefit remain only partially understood. Since previous studies of whole allergen immunotherapy demonstrated a reduction in the frequency of allergen-specific (MHC II tetramer+ ) CD4+ T cells expressing the chemokine receptor CRTh2, we assessed the impact of Cat-PAD on the frequency and functional phenotype of Fel d 1-specific CD4+ T cells.

Methods: Using before and after treatment samples from subjects enrolled in a randomized, double-blind, placebo-controlled trial of Cat-PAD, we employed Fel d 1 MHC II tetramers and flow cytometry to analyze the expression of chemokine receptors CCR3, CCR4, CCR5, CXCR3, and CRTh2, together with markers of memory phenotype (CD27 and CCR7) on Fel d 1-specific CD4+ T cells.

Results: No statistically significant change in the frequency of Fel d 1-specific CD4+ T cells, nor in their expression of chemokine receptors or memory phenotype, was observed. However, a significant reduction in cell surface expression of CRTh2 was observed between the placebo and active groups (P = 0.047).

Conclusions: Peptide immunotherapy with Cat-PAD does not significantly alter the frequency or phenotype of Fel d 1-CD4+ T cells, but may decrease their expression of CRTh2.

Keywords: T cells; chemokines; immunotherapy and tolerance induction; immunotherapy vaccines and mechanisms; vaccines.

Publication types

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

MeSH terms

  • Allergens / immunology*
  • Animals
  • Cats
  • Desensitization, Immunologic
  • Epitopes, T-Lymphocyte / immunology*
  • Gene Expression Regulation*
  • Glycoproteins / immunology
  • Humans
  • Immunologic Memory
  • Immunomodulation / genetics*
  • Lymphocyte Count
  • Peptides / administration & dosage
  • Peptides / immunology*
  • Receptors, Immunologic / genetics*
  • Receptors, Prostaglandin / genetics*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Allergens
  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • Peptides
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Fel d 1 protein, Felis domesticus
  • prostaglandin D2 receptor