title: Birch pollen immunotherapy results in long-term loss of Bet v 1-specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies.
abstract: BACKGROUND
  Early events of specific immunotherapy (SIT) are induction of allergen-specific IL-10-producing T(R)1 cells and production of IgG antibodies, but there is little knowledge about the long-term immune mechanisms responsible for sustained allergen tolerance.
  
  
  OBJECTIVE
  Bet v 1-specific immune responses of 16 patients with birch pollen allergy were characterized up to 54 months at defined time points before, during, and after a 3-year period of SIT.
  
  
  METHODS
  We sought to analyze allergen-specific T- and B-cell responses. Bet v 1-specific IL-5-, IFN-γ-, and IL-10-secreting T cells were quantified in peripheral blood, and birch pollen-specific IgE and IgG antibody levels were determined in serum. Furthermore, the inhibitory capacity of SIT-induced IgG was evaluated by blocking allergen binding to IgE and inhibition of facilitated allergen presentation.
  
  
  RESULTS
  Seasonal increases in Bet v 1-specific T(H)2 cell numbers ceased to appear after the first year of SIT without deviation to a T(H)1-dominated immune response. Furthermore, the frequency of IL-10-producing T(R)1 cells, which had increased during the first year of SIT, returned to pretreatment levels in the second year. In contrast, allergen-specific IgG antibody concentrations continuously increased during SIT but started to decrease after cessation of treatment. Functional analysis confirmed the ability of the IgG antibodies to inhibit IgE-allergen interactions, which peaked at the end of SIT but then slowly started to decrease.
  
  
  CONCLUSIONS
  Long-term allergen tolerance achieved by SIT is associated with the development of peripheral T-cell tolerance characterized by decreased reactivity of Bet v 1-specific T(H)2 cells and enriched allergen-specific IgG competing with IgE antibodies for allergen binding.
authors.affiliation: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Möbs
authors.forename: Henrik
authors.initials: H
authors.lastname: Ipsen
authors.forename: Lea
authors.initials: L
authors.lastname: Mayer
authors.forename: Caroline
authors.initials: C
authors.lastname: Slotosch
authors.forename: Arnd
authors.initials: A
authors.lastname: Petersen
authors.forename: Peter A
authors.initials: PA
authors.lastname: Würtzen
authors.forename: Michael
authors.initials: M
authors.lastname: Hertl
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pfützner
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D052179:Antigens, Plant / Q000009:adverse effects / Q000276:immunology*; D029662:Betula / Q000276:immunology*; D001667:Binding, Competitive; D016207:Cytokines / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000379:methods*; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011058:Pollen / Q000009:adverse effects / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D007074:Immunoglobulin G; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E