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

Abstract

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. 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. 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). 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.