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

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BACKGROUND: The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT). OBJECTIVES: 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.