title: Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity.
abstract: BACKGROUND
  Grass pollen immunotherapy is an effective treatment for seasonal allergic rhinitis that provides the opportunity to study the induction and maintenance of allergen-specific immune tolerance.
  
  
  OBJECTIVE
  We investigated the relationship between clinical responsiveness, regulatory cytokine production, and antibody responses to allergen during 1 year of immunotherapy.
  
  
  METHODS
  Eighteen subjects with severe seasonal allergic rhinitis were randomized double-blind to receive active or placebo injections of an alum-adsorbed grass pollen vaccine (Alutard SQ). Subjects underwent repeated testing of early- and late-phase skin responses to intradermal allergen, and cellular responses to grass pollen allergen were tested. Sera were tested for allergen-specific IgG4, IgA, and inhibitory activity in biologic assays of IgE responses.
  
  
  RESULTS
  Grass pollen immunotherapy was effective in reducing overall symptom scores (P < .05) and conjunctival reactivity (P < .05). In the active group significant IL-10 production occurred early at low allergen doses and at a similar time as inhibition of late skin responses at 2 to 4 weeks. Serum allergen-specific IgG4, IgA, and inhibitory antibody activity for basophil histamine release and IgE-facilitated allergen binding to B cells occurred later, at 6 to 12 weeks, at higher allergen doses and preceded inhibition of early skin responses.
  
  
  CONCLUSIONS
  IL-10 responses occur early but at immunotherapy doses that are not clinically effective. Later induction of inhibitory antibodies, including IgG4 and IgA, might be required for efficacy through modulation of IgE-mediated events.
authors: Allergy and Clinical Immunology Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: James N
authors: JN
authors: Francis
authors: Louisa K
authors: LK
authors: James
authors: Giannis
authors: G
authors: Paraskevopoulos
authors: Cheukyee
authors: C
authors: Wong
authors: Moises A
authors: MA
authors: Calderon
authors: Stephen R
authors: SR
authors: Durham
authors: Stephen J
authors: SJ
authors: Till
mesh_terms: D000328:Adult; D003888:Desensitization, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D008297:Male; D010919:Placebos; D010936:Plant Extracts / Q000276:immunology / Q000627:therapeutic use; D006109:Poaceae / Q000737:chemistry / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000517:prevention & control*; D012882:Skin Tests; D013995:Time
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010919:Placebos; D010936:Plant Extracts; D016753:Interleukin-10; D007073:Immunoglobulin E