26 different compounds have been investigated experimentally for their sensitizing capacity in guinea pigs. 19 of these occur in propolis as well as in poplar bud exudates, and 14 of them are also found in balsam of Peru. 4 caffeates and benzyl isoferulate were found to be strong sensitizers. 7 compounds were moderate, and 13 compounds showed only weak sensitizing potency. Methyl cinnamate was negative. Patch tests in 11 propolis-sensitive patients once more revealed 3-methyl-2-butenyl caffeate and phenylethyl caffeate as the major sensitizers. In addition to the 8 compounds already known to occur in propolis as well as in balsam of Peru, we detected 5 further substances that both materials have in common. Among these, benzyl isoferulate is considered a noteworthy sensitizer. Coniferyl benzoate, which was shown to be a moderate sensitizer, is present in fresh samples of balsam of Peru, while in propolis it has been detected only once so far. The flavonoid aglycones occurring in poplar bud exudates, and hence also in propolis, are weak sensitizers which play only a minor role in propolis hypersensitivity.

The use of allergoids for allergen-specific immunotherapy has been established for many years. The characteristic features of these chemically modified allergens are their strongly reduced IgE binding activity compared with the native form and the retained immunogenicity. T cell reactivity of chemically modified allergens is documented in animals, but in humans indirect evidence of reactivity has been concluded from the induction of allergen-specific IgG during immunotherapy. Direct evidence of T cell reactivity was obtained recently using isolated human T cells. To obtain further insight into the mechanism of action of allergoids, we compared the Ag-presenting capacity of different APC types, including DC and macrophages, generated from CD14+ precursor cells from the blood of grass pollen allergic subjects, autologous PBMC, and B cells. These APC were used in experiments together with Phl p 5-specific T cell clones under stimulation with grass pollen allergen extract, rPhl p 5b, and the respective allergoids. Using DC and macrophages, allergoids exhibited a pronounced and reproducible T cell-stimulating capacity. Responses were superior to those with PBMC, and isolated B cells failed to present allergoids. Considerable IL-12 production was observed only when using the DC for Ag presentation of both allergens and allergoids. The amount of IL-10 in supernatants was dependent on the phenotype of the respective T cell clone. High IL-10 production was associated with suppressed IL-12 production from the DC in most cases. In conclusion, the reactivity of Th cells with allergoids is dependent on the type of the APC.

Background: Successful allergen–specific immunotherapy is achieved with progressively increasing doses of allergen or allergoid. In order to gain further insight into the mechanism of action of allergoids several in vitro investigations were conducted. Methods: Peripheral blood mononuclear cells (PBMC) from grass pollen allergic and nonallergic subjects were stimulated with either grass pollen extract or allergoid and the proliferation and cytokine production (IL–5, IFN–γ) were measured. Similar investigations were performed with Phl p 5–specific T cell lines (TCL) and clones (TCC). Dendritic cells and PBMC were compared in terms of their relative efficacies as antigen–presenting cells. Results: Both allergen and allergoid induced proliferation and Th2 and Th1 cytokine synthesis by PBMC of allergic subjects, whereas PBMC of nonallergic subjects did not produce IL–5. The maximum level of IL–5 was obtained with a lower concentration than was necessary for maximal IFN–γ production. Higher stimulation doses of allergen and allergoid shifted the cytokine profiles towards a Th1 phenotype. TCL and TCC clearly showed reactivity with both allergen and allergoid when using autologous PBMC for antigen presentation, but compared with the native allergen the reactivity of the allergoid was reduced with most of the TCC. Using dendritic cells for antigen presentation a pronounced increase of stimulation of the TCC especially for the allergoids becomes obvious. Conclusion: In common with grass pollen allergen the corresponding allergoids possess a strong allergen–specific T cell–stimulating capacity. However, the degree of T cell stimulation by the allergoid seems to be dependent on the type of the antigen–presenting cell. Both, allergen and allergoid, can modulate T cell responses in a dose–dependent manner.

No abstract

No abstract