Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity

J Allergy Clin Immunol. 2008 May;121(5):1120-1125.e2. doi: 10.1016/j.jaci.2008.01.072. Epub 2008 Apr 18.


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.

Objectives: 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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Desensitization, Immunologic*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Male
  • Placebos
  • Plant Extracts / immunology
  • Plant Extracts / therapeutic use
  • Poaceae / chemistry
  • Poaceae / immunology
  • Rhinitis, Allergic, Seasonal / blood
  • Rhinitis, Allergic, Seasonal / prevention & control*
  • Skin Tests
  • Time


  • Immunoglobulin A
  • Immunoglobulin G
  • Placebos
  • Plant Extracts
  • Interleukin-10
  • Immunoglobulin E