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 (P < 0.001) were observed, as well as a decrease in the frequency of potential “pro‐allergic” CD27‐ Th2 cells from patients receiving active tablets (P < 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.