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A Novel Approach to Specific Allergy Treatment: The Recombinant Allergen-S-Layer Fusion Protein rSbsC-Bet v 1 Matures Dendritic Cells That Prime Th0/Th1 and IL-10-Producing Regulatory T Cells¹

Marianne Gerstmayr^*, Nicola Ilk, Irma Schabussova^*, Beatrice Jahn-Schmid^*, Eva M. Egelseer, Uwe B. Sleytr, Christof Ebner and Barbara Bohle^2,*

^* Department of Pathophysiology, Center for Physiology, Pathophysiology, and Immunology, Medical University of Vienna, Vienna, Austria; and Center for NanoBiotechnology, University of Natural Resources and Applied Life Sciences and Allergy Clinic Reumannplatz, Vienna, Austria

An ideal vaccine for allergen-specific immunotherapy of type I allergies should display reduced mediator-releasing capacity, induce maturation of APC, and modify the disease-eliciting Th2-dominated allergen-specific response to a more physiological response. We have previously shown that rSbsC-Bet v 1, the recombinant fusion protein of a bacterial surface (S-layer) protein of Geobacillus stearothermophilus ATCC 12980 and the major birch pollen allergen Bet v 1, exhibited reduced allergenicity and induced IFN- and IL-10 synthesis in Bet v 1-specific Th2 clones. In this study, we characterized the effects of rSbsC-Bet v 1 on immature monocyte-derived dendritic cells (mdDC) and the consequences for the polarization of naive CD4⁺ T lymphocytes isolated from the blood of birch pollen-allergic patients. mdDC responded to rSbsC-Bet v 1 with a significant up-regulation of costimulatory molecules, functional maturation, and the synthesis of IL-10 and IL-12. mdDC matured with rSbsC-Bet v 1 induced the differentiation of naive T cells into IFN--producing cells. This effect was IL-12 dependent. In parallel, a substantial number of naive T cells developed into IL-10-producing CD25⁺Foxp3⁺CLTA-4⁺ cells capable of active suppression. Thus, rSbsC-Bet v 1 showed immune stimulatory capacity on DC, which then promoted the simultaneous differentiation of Th0/Th1 cells and regulatory T cells. These data further support that the concept of conjugating allergens to bacterial agents is a promising approach to improve vaccines for specific immunotherapy of atopic allergies.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung (SFB-F1807-B04); P12158 by the OeNB, Austria; P18510-B12 by the European Union Project NAS-SAP; and by the U.S. Air Force Office of Scientific Research, Project FA9550-07-1-0313.

² Address correspondence and reprint requests to Dr. Barbara Bohle, Department of Pathophysiology, Center for Physiology, Pathophysiology, and Immunology, Medical University of Vienna, Austria; AKH-3Q, Waehringer Guertel 18-20, Vienna, Austria. E-mail address: barbara.bohle{at}meduniwien.ac.at

³ Abbreviations used in this paper: SIT, specific immunotherapy; DC, dendritic cell; mdDC, monocyte-derived DC; B-DC, mdDC incubated with rBet v 1; CpG-ODN, oligodeoxynucleotides containing CpG motifs; Ct, threshold cycle; LB-CD, mdDC incubated with LPS and rBet v 1; SB-DC, mdDC incubated with rSbsC-Bet b 1; Treg, T regulatory.