Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice

Soheila Shirinbak, Yousef A. Taher, Hadi Maazi, Renee Gras, Betty C. A. M. van Esch, Paul A. J. Henricks, Janneke N. Samsom, J. Sjef Verbeek, Bart N. Lambrecht, Antoon J. M. van Oosterhout*, Martijn C. Nawijn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

Allergen-specific immunotherapy (IT) uniquely renders long-term relief from allergic symptoms and is associated with elevated serum levels of allergen-specific IgG and IgA. The allergen-specific IgG response induced by IT treatment was shown to be critical for suppression of the immediate phase of the allergic response in mice, and this suppression was partially dependent on signaling through Fc gamma RIIB. To investigate the relevance of the allergen-specific IgG responses for suppression of the Th2-driven late-phase allergic response, we performed IT in a mouse model of allergic asthma in the absence of FcgRIIB or Fc gamma RI/Fc gamma RIII signaling. We found that suppression of Th2 cell activity, allergic inflammation, and allergen-specific IgE responses is independent of Fc gamma RIIB and Fc gamma RI/Fc gamma RIII signaling. Moreover, we show that the IT-induced allergen-specific systemic IgG or IgA responses and B cell function are dispensable for suppression of the late-phase allergic response by IT treatment. Finally, we found that the secretory mucosal IgA response also is not required for suppression of the Th2-driven allergic inflammation by IT. These data are in contrast to the suppression of the immediate phase of the allergic response, which is critically dependent on the induced allergen-specific serum IgG response. Hence, IT-induced suppression of the immediate and late phases of the allergic response is governed by divergent and independent mechanisms. Our data show that the IT-induced suppression of the Th2 cell-dependent late-phase allergic response is independent of the allergen-specific IgG and IgA responses that are associated with IT treatment. The Journal of Immunology, 2010, 185: 3857-3865.

Original languageEnglish
Pages (from-to)3857-3865
Number of pages9
JournalJournal of Immunology
Volume185
Issue number7
DOIs
Publication statusPublished - 1-Oct-2010

Keywords

  • GRASS-POLLEN IMMUNOTHERAPY
  • FC-GAMMA-RIIB
  • DEFICIENT MICE
  • MURINE MODEL
  • TGF-BETA
  • BLOCKING ANTIBODY
  • DENDRITIC CELLS
  • MOUSE MODEL
  • TOLERANCE
  • EXPRESSION

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