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Clinical & Experimental Allergy

Allergen-specific CD4+ T cell responses in peripheral blood do not predict the early onset of clinical efficacy during grass pollen sublingual immunotherapy

Authors


Correspondence:

Philippe Moingeon, Research and Development, Stallergenes, 6 rue Alexis de Tocqueville, 92160 Antony, France.

E-mail: pmoingeon@stallergenes.com

Summary

Background

Surrogate biomarkers of efficacy are needed in support of allergen-specific immunotherapy.

Objective

The aim of this study was to relate changes in peripheral CD4+ T cell responses to clinical efficacy during sublingual immunotherapy (SLIT).

Methods

Allergen-specific CD4+ T cell responses were assessed in peripheral blood mononuclear cells (PBMCs) from 89 grass pollen-allergic individuals enrolled in a double-blind placebo-controlled SLIT study conducted in an allergen exposure chamber (ClinicalTrials.gov NCT00619827). Surface phenotype, proliferative responses, cytokine production and gene expression were analysed in coded samples at baseline, and after 2 and 4 months of SLIT, in PBMCs after in vitro allergen stimulation or among MHC class II/peptide (pMHCII)-tetramer-positive CD4+ T cells.

Results

SLIT induced a 29.3% improvement of the average rhinoconjunctivitis total symptom score in the active group, when compared to the placebo group. In parallel, only minor changes in proportions of CD4+ T cells expressing Th1 (CCR5+, CXCR3+), Th2 (CRTh2+, CCR4+) and Treg (CD25+, CD127-, Foxp3+) markers were detected. A down-regulation of IL-4 and IL-10 gene expression and IL-10 secretion (< 0.001) were observed, as well as a decrease in the frequency of potential “pro-allergic” CD27- Th2 cells from patients receiving active tablets (< 0.001), but without any correlation with clinical benefit. pMHCII-tetramer analyses failed to document any major impact in both numbers and polarization of circulating Phl p 1- and Phl p 5-specific CD4+ T cells, confirming that early clinical improvement during SLIT is not associated with dramatic alterations in T lymphocyte responses.

Conclusion & Clinical Relevance

Changes in patterns of peripheral CD4+ T cells are not markers for the early onset of efficacy during SLIT.

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