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

Abstract

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. We investigated the relationship between clinical responsiveness, regulatory cytokine production, and antibody responses to allergen during 1 year of immunotherapy. 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. 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. 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.