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Counterregulating the disease-eliciting Th2-like immune response of allergen-specific Th lymphocytes by fostering an allergen-specific Th1-like response is a promising concept for future immunotherapy of type I allergy. The use of recombinant allergens combined with more functional adjuvants has been proposed. In this respect, we present a novel approach. The gene sequence encoding the major birch pollen allergen, Bet v 1, was fused with the gene encoding the bacterial cell surface (S-layer) protein of Geobacillus stearothermophilus, resulting in the recombinant protein, rSbsC-Bet v 1. rSbsC-Bet v 1 contained all relevant Bet v 1-specific B and T cell epitopes, but was significantly less efficient to release histamine than rBet v 1. In cells of birch pollen-allergic individuals, rSbsC-Bet v 1 induced IFN-γ along with IL-10, but no Th2-like response, as observed after stimulation with Bet v 1. Intracellular cytokine staining revealed that rSbsC-Bet v 1 promoted IFN-γ-producing Th cells. Moreover, rSbsC-Bet v 1 induced IFN-γ synthesis in Bet v 1-specific Th2 cell clones, and importantly, increased IL-10 production in these cells. In conclusion, genetic fusion of an allergen to S-layer proteins combined reduced allergenicity with immunomodulatory capacity. The strategy described in this work may be generally applied to design vaccines for specific immunotherapy of type I allergy with improved efficacy and safety.

Systemic lupus erythematosus (SLE) represents an autoimmune disease for which alterations of T cells, B cells as well as various antigen-presenting cell (APC) populations have been described. In order to better define APC-associated deficiencies, we analyzed morphologic, phenotypic and functional characteristics of in vitro-generated monocyte-derived dendritic cells (MoDC) from SLE patients as compared with healthy controls. Analysis of MoDC at different stages of maturation revealed substantial phenotypic and functional defects of MoDC from SLE patients as compared with healthy controls. In particular, we observed a significantly reduced up-regulation of MHC class II molecules on MoDC upon activation which correlated with disease activity scores and functional deficiencies in mixed lymphocyte reaction experiments. Our data imply a crucial role of APC in the immunological imbalance in SLE for foreign and self-antigen reactivity.