title: Allergen-specific CD4+ T cell responses in peripheral blood do not predict the early onset of clinical efficacy during grass pollen sublingual immunotherapy.
abstract: 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.
  
  
  CONCLUSIONS
  Changes in patterns of peripheral CD4(+) T cells are not markers for the early onset of efficacy during SLIT.
authors.affiliation: Stallergenes, Antony, France.
authors.forename: M
authors.initials: M
authors.lastname: Bonvalet
authors.forename: H
authors.initials: H
authors.lastname: Moussu
authors.forename: E
authors.initials: E
authors.lastname: Wambre
authors.forename: C
authors.initials: C
authors.lastname: Ricarte
authors.forename: S
authors.initials: S
authors.lastname: Horiot
authors.forename: A-C
authors.initials: AC
authors.lastname: Rimaniol
authors.forename: W W
authors.initials: WW
authors.lastname: Kwok
authors.forename: F
authors.initials: F
authors.lastname: Horak
authors.forename: O
authors.initials: O
authors.lastname: de Beaumont
authors.forename: V
authors.initials: V
authors.lastname: Baron-Bodo
authors.forename: P
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D000286:Administration, Sublingual; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology*; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D011237:Predictive Value of Tests; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; C470842:Phlp 5b allergen, timothy grass; D010940:Plant Proteins; C090396:PHLPI protein, Phleum pratense