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

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. Peptide immunotherapy with Cat‐PAD reduces the surface expression of Chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTh2) on Fel d 1‐specific T cells. Neither the frequency, nor memory phenotype of Fel d 1‐specific T cells in the blood were affected by peptide immunotherapy for cat allergy. Reduced expression of CRTh2 may modulate recruitment to sites of allergen exposure.