Birch pollen immunotherapy results in long-term loss of Bet v 1-specific T(H)2 responses, transient T(R)1 activation, and synthesis of IgE-blocking antibodies

作者：Moebs Christian; Ipsen Henrik; Mayer Lea; Slotosch Caroline; Petersen Arnd; Wurtzen Peter A; Hertl Michael; Pfuetzner Wolfgang

来源：Journal of Allergy and Clinical Immunology, 2012, 130(5): 1108-+.

DOI：10.1016/j.jaci.2012.07.056

• Respiratory allergy
• specific immunotherapy
• allergen tolerance
• Bet v 1
• IgE
• IgG
• blocking antibodies
• regulatory T cells

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. %26lt;br%26gt;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. %26lt;br%26gt;Methods: We sought to analyze allergen-specific T- and B-cell responses. Bet v 1-specific IL-5-, IFN-gamma-, and IL-10-secreting T cells were quantified in peripheral blood, and birch pollenspecific 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. %26lt;br%26gt;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 TH1-dominated immune response. Furthermore, the frequency of IL-10-producing TR1 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. %26lt;br%26gt;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 TH2 cells and enriched allergen-specific IgG competing with IgE antibodies for allergen binding. (J Allergy Clin Immunol 2012; 130: 1108-16.)

• 出版日期2012-11