1. ¹Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
2. ²Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
3. ³Department of Respiratory Diseases, Laboratory of Immunoregulation and Mucosal Immunology, University of Ghent, Ghent, Belgium
4. ⁴Department of Cell Biology & Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
5. ⁵Bioceros B.V., Utrecht, The Netherlands
6. ⁶Laboratory of Mucosal Immunity, Unit of Pneumology/Microbiology, Université catholique de Louvain, Brussels, Belgium
7. ⁷Institute of Pathology, University of Oslo, Oslo, Norway
8. ⁸These authors contributed equally to the work.

Correspondence: BN Lambrecht, (Bart.Lambrecht@UGent.be)

Received 3 November 2008; Accepted 1 April 2009; Published online 29 April 2009.

Abstract

In healthy individuals, humoral immune responses to allergens consist of serum IgA and IgG4, whereas cellular immune responses are controlled by regulatory T (Treg) cells. In search of new compounds that might prevent the onset of allergies by stimulating this type of immune response, we have focused on the mucosal adjuvant, cholera toxin B (CTB), as it induces the formation of Treg cells and production of IgA. Here, we have found that CTB suppresses the potential of dendritic cells to prime for Th2 responses to inhaled allergen. When we administered CTB to the airways of naïve and allergic mice, it strongly suppressed the salient features of asthma, such as airway eosinophilia, Th2 cytokine synthesis, and bronchial hyperreactivity. This beneficial effect was only transferable to other mice by transfer of B but not of T lymphocytes. CTB caused a transforming growth factor--dependent rise in antigen-specific IgA in the airway luminal secretions, which was necessary for its preventive and curative effect, as all effects of CTB were abrogated in mice lacking the luminal IgA transporting polymeric Ig receptor. Not only do these findings show a novel therapeutic avenue for allergy, they also help to explain the complex relationship between IgA levels and risk of developing allergy in humans.