title: Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation.
abstract: Allergen-specific CD4+ T lymphocytes are activated at extremely low allergen concentrations in vivo as a result of serum-facilitated allergen presentation (S-FAP). It is not clear at present if specific allergy vaccination (SAV) has an effect on this mechanism. Here we show that birch allergen-specific serum-IgE facilitates the presentation of Bet v 1, the major birch pollen allergen, to Bet v 1-specific CD4+ T lymphocytes by a factor of >100. This process is CD23 mediated, could be detected in sera from the majority of birch-allergic patients, and was clearly dose dependent. S-FAP of Bet v 1 was inhibited in patients undergoing long-term birch SAV, but not by sera from patients undergoing grass SAV, indicating that birch-specific Abs are involved. This resulted in decreased proliferation and IL-4, IL-5, IL-10, and IFN-gamma production of Bet v 1-specific T cells. The inhibition was already noted after 3-9 mo of SAV and could not be solely explained by increased serum levels of birch-specific IgG4. When IgG- and IgA/IgM-containing fractions of long-term SAV sera were used to inhibit S-FAP, only IgG-containing fractions were shown to inhibit S-FAP. These results indicate that blocking IgG Abs induced by SAV inhibits the occurrence of S-FAP at very low allergen concentrations, resulting in significantly higher allergen threshold levels to obtain T cell proliferation and cytokine production and thus allergen-induced late-phase responses.
authors.affiliation: ALK-Abelló, Horsholm, Denmark; and Lung and Allergy Clinic, Copenhagen, Denmark. joost-vanneerven@tanox.nl
authors.forename: R J
authors.initials: RJ
authors.lastname: van Neerven
authors.forename: T
authors.initials: T
authors.lastname: Wikborg
authors.forename: G
authors.initials: G
authors.lastname: Lund
authors.forename: B
authors.initials: B
authors.lastname: Jacobsen
authors.forename: A
authors.initials: A
authors.lastname: Brinch-Nielsen
authors.forename: J
authors.initials: J
authors.lastname: Arnved
authors.forename: H
authors.initials: H
authors.lastname: Ipsen
mesh_terms: D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D019138:Antibodies, Blocking / Q000096:biosynthesis* / Q000502:physiology*; D017951:Antigen Presentation / Q000276:immunology*; D018941:Antigens, CD19 / Q000276:immunology; D052179:Antigens, Plant; D001831:Body Temperature; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003888:Desensitization, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000502:physiology; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology / Q000502:physiology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D010940:Plant Proteins / Q000276:immunology* / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology; D014197:Trees / Q000276:immunology
chemical_list: D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D019138:Antibodies, Blocking; D018941:Antigens, CD19; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D007106:Immune Sera; D007074:Immunoglobulin G; D010940:Plant Proteins; D017455:Receptors, IgE; C026408:anti-IgE antibodies; C048844:anti-IgG; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E