Decrease of IL-5 Production by Naive T Cells Cocultured with IL-18-Producing BCG-Pulsed Dendritic Cells from Patients Allergic to House Dust Mite.

The only currently available anti-tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), has been reported to also protect against unrelated diseases, including inflammatory diseases such as allergic asthma. Recombinant BCG strains that produce IL-18 have been shown to enhance Th1 responses over non-recombinant BCG and to reduce IL-5 production and bronchoalveolar eosinophilia in mice. However, their ability to decrease the immune polarization of human Th2 cells is not known. Here, we show that BCG and recombinant BCG producing human IL-18 (rBCG-hIL-18) induced the maturation of Der p 1-stimulated monocyte-derived dendritic cells (MD-DCs) from healthy controls and from patients allergic to house dust mites. After incubation with mycobacteria and Der p 1, MD-DCs produced significantly more IL-23 and IP-10 but had no effect on IL-12p70 or IL-10 production compared to Der p 1-pulsed MD-DCs in the absence of mycobacteria. In the presence of Der p 1, BCG- and rBCG-hIL-18-pulsed MD-DCs cocultured with naive, but not with memory T cells from allergic patients, resulted in a decrease in IL-5 production compared to non-pulsed MD-DCs cultured in the presence of Der p 1. BCG, and especially rBCG-hIL-18, may thus be potential therapeutic tools to reduce exacerbated Th2 responses in patients with allergic asthma.

Association between Venom Immunotherapy and Changes in Serum Protein-Peptide Patterns.

Venom immunotherapy (VIT) is administered to allergic patients to reduce the risk of dangerous systemic reactions following an insect sting. To better understand the mechanism of this treatment and its impact on the human organism, we analysed serum proteomic patterns obtained at five time-points from Hymenoptera-venom-allergic patients undergoing VIT. For statistical analyses, patients were additionally divided into two groups (high responders and low responders) according to serum sIgG4 levels. VIT was found to be associated with changes in seven proteins: the fibrinogen alpha chain, complement C4-A, complement C3, filamin-B, kininogen-1, myosin-9 and inter-alpha-trypsin inhibitor heavy chain H1. The number of discriminative m/z (mass-to-charge ratio) features increased up to the 90th day of VIT, which may be associated with the development of immunity after the administration of increased venom doses. It may also suggest that during VIT, there may occur processes involved not only in protein synthesis but also in protein degradation (caused by proteolytic venom components). The results are consistent with measured serum sIgG4 levels, which increased from 2.04 mgA/I at baseline to 7.25 mgA/I at 90 days. Moreover, the major proteomic changes were detected separately in the high responder group. This may suggest that changes in protein-peptide profiles reflect the actual response to VIT.