Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4(+) T cells by inhibiting serum-IgE-facilitated allergen presentation

Allergen-specific CD4(+) T lymphocytes are activated at extremely low aller gen concentrations in vivo as a result of serum-facilitated allergen presen tation (S-FAP), It is not clear at present if specific allergy vaccination (SAV) has an effect on this mechanism. Here Ive show that birch allergen-sp ecific serum-IgE facilitates the presentation of Bet v 1, the major birch p ollen allergen, to Bet v I-specific CD4(+) T lymphocytes by a factor of >10 0. This process is CD23 mediated, could be detected in sera from the majori ty 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 s era from patients undergoing grass SAV, indicating that birch-specific Abs are involved, This resulted in decreased proliferation and IL-4, IL-5, IL-1 0, 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 inc reased serum levels of birch-specific IgG4, When IgG- and IgA/IgM-containin g fractions of long-term SAV sera were used to inhibit S-FAP, only IgG-cont aining fractions were shown to inhibit S-FAP, These results indicate that b locking IgG Abs induced by SAV inhibits the occurrence of S-PAP at very low allergen concentrations, resulting in significantly higher allergen thresh old levels to obtain T cell proliferation and cytokine production and thus allergen-induced late-phase responses.