Abstract
An effective specific immunotherapy should contain elements to generate specific recognition (T-cell peptides) and to modulate the immunological response towards a Th1/Treg pattern by enhancing dendritic cells (DCs). We propose a novel sublingual immunotherapy for peach allergy, using systems, that combine Prup3-T-cell peptides with mannose dendrons (D1ManPrup3 and D4ManPrup3). Peach anaphylactic mice were treated 1, 2 and 5 nM concentrations. Tolerance was assessed one/five weeks after finishing treatment by determining in vivo/in vitro parameters after challenge with Prup3. Only mice receiving D1ManPrup3 at 2 nM were protected from anaphylaxis (no temperature changes, decrease in Prup3-sIgE and -sIgG1 antibody levels, and secreting cells) compared to PBS-treated mice. Moreover, an increase of Treg-cells and regulatory cytokines (IL-10+/IFN-γ+) in CD4+-T-cells and DCs were found. These changes were maintained at least five weeks after stopping treatment. D1ManPrup3 is an effective new approach of immunotherapy inducing protection from anaphylaxis which persists after finishing treatment.
Highlights
An effective specific immunotherapy should contain elements to generate specific recognition (T-cell peptides) and to modulate the immunological response towards a Th1/Treg pattern by enhancing dendritic cells (DCs)
These changes are orchestrated by dendritic cell (DCs) that modulate the response towards a Th1 pattern, and the generation of FoxP3+ regulatory T cells (Treg), which develop their suppressive activity mainly by the induction of IL-10+ Treg cells[9,10,11]
One potential factor for the current lack of allergen specific immunotherapy (AIT) efficacy may be related to allergen concentration
Summary
An effective specific immunotherapy should contain elements to generate specific recognition (T-cell peptides) and to modulate the immunological response towards a Th1/Treg pattern by enhancing dendritic cells (DCs). For LTP allergy, sublingual immunotherapy (SLIT) with the major peach allergen, Prup[3], produces clinically beneficial effects for mild, moderate, and even severe reactions[7,8,9,10]. Studies of the immunological events associated with the tolerant response induced by SLIT have found increases of allergen-specific IgG4 (sIgG4) and decreases of allergen-specific IgE (sIgE) and effector T cells (Th2 and Th9). These changes are orchestrated by dendritic cell (DCs) that modulate the response towards a Th1 pattern, and the generation of FoxP3+ regulatory T cells (Treg), which develop their suppressive activity mainly by the induction of IL-10+ Treg cells[9,10,11]. Correspondence and requests for materials should be addressed to C.M.
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