Allergen-specific CD4+ T cell responses in peripheral blood do not predict the early onset of clinical efficacy during grass pollen sublingual immunotherapy
Article first published online: 26 NOV 2012
© 2012 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 42, Issue 12, pages 1745–1755, December 2012
How to Cite
Cite this as: Clinical & Experimental Allergy 2012 (42) 1745–1755., , , , , , , , , , ,
- Issue published online: 26 NOV 2012
- Article first published online: 26 NOV 2012
- Accepted manuscript online: 28 SEP 2012 07:01AM EST
- Manuscript Accepted: 1 AUG 2012
- Manuscript Revised: 19 JUL 2012
- Manuscript Received: 15 MAY 2012
- French Association Nationale de la Recherche et de la Technologie
- CD4+ T lymphocyte;
- grass pollen;
- MHC class II tetramers;
- sublingual immunotherapy
Surrogate biomarkers of efficacy are needed in support of allergen-specific immunotherapy.
The aim of this study was to relate changes in peripheral CD4+ T cell responses to clinical efficacy during sublingual immunotherapy (SLIT).
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.
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.