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  • 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.
    Author: Möbs C, Ipsen H, Mayer L, Slotosch C, Petersen A, Würtzen PA, Hertl M, Pfützner W.
    Journal: J Allergy Clin Immunol; 2012 Nov; 130(5):1108-1116.e6. PubMed ID: 23021882.
    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. CONCLUSION: 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.
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