title: Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells.
abstract: BACKGROUND
  The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT).
  
  
  OBJECTIVE
  To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB).
  
  
  METHODS
  Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebo-treated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-beta mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT.
  
  
  RESULTS
  Foxp3(+) cells were increased in the oral epithelium of SLIT- vs. placebo-treated atopics (P=0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P=0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT- compared with placebo-treated atopics (P=0.1 for both). IgG(1) and IgG(4) were increased following SLIT (P<0.001). Peak seasonal IgA(1) and IgA(2) were increased during SLIT (P<0.05). There was a time-dependent increase in serum inhibitory activity for IgE-FAB in SLIT-treated atopics.
  
  
  CONCLUSIONS
  SLIT with grass pollen extract is associated with increased Foxp3(+) cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.
authors.affiliation: National Heart and Lung Institute, Imperial College London, UK.
authors.forename: G W
authors.initials: GW
authors.lastname: Scadding
authors.forename: M H
authors.initials: MH
authors.lastname: Shamji
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobson
authors.forename: D I
authors.initials: DI
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Wilson
authors.forename: M T
authors.initials: MT
authors.lastname: Lima
authors.forename: L
authors.initials: L
authors.lastname: Pitkin
authors.forename: C
authors.initials: C
authors.lastname: Pilette
authors.forename: K
authors.initials: K
authors.lastname: Nouri-Aria
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D000485:Allergens / Q000276:immunology; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology; D031784:Phleum / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007073:Immunoglobulin E