A novel role for neutrophils in IgE-mediated allergy: evidence for antigen-presentation in late-phase reactions

Publication date: Available online 18 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Dominika Polak, Christine Hafner, Peter Briza, Claudia Kitzmüller, Adelheid Elbe-Bürger, Nazanin Samadi, Maria Gschwandtner, Wolfgang Pfützner, Gerhard J. Zlabinger, Beatrice Jahn-Schmid, Barbara Bohle
BackgroundNeutrophils and allergen-specific T-cells accumulate in allergic late-phase reactions (LPR). Their presence is associated with severe inflammation. Cytokines like GM-CSF, IFN-γ, and IL-3, typically found in allergic LPR, have been proposed to convert neutrophils into antigen-presenting cells (APC).ObjectiveTo assess the antigen-processing and presenting capacity of neutrophils from allergic patients.MethodsNeutrophils were isolated from peripheral blood of birch pollen-allergic donors and stimulated with GM-CSF, IFN-γ, and IL-3. Viability and expression of HLA-DR, CD80, and CD86 were assessed by flow cytometry. HLA-DM expression was analysed by immunoblotting. Allergen-uptake was studied with fluorescence-labelled major birch pollen allergen Bet v 1. Bet v 1 was digested with neutrophilic endolysosomal extracts and resulting fragments were sequenced using mass spectrometry. Neutrophils were used as APC in co-culture experiments with autologous HLA-DR-restricted Bet v 1-specific T-cell clones reactive with epitopes in different regions of the allergen. In all experiments, monocytes were used for comparison. Fluids from suction blisters formed on top of LPR induced by intradermal allergen injection were assessed for HLA-DR-positive neutrophils by flow cytometry.ResultsThe cytokines significantly enhanced the survival, allergen uptake and expression of HLA-DM and HLA-DR of neutrophils. Neutrophils rapidly degraded Bet v 1 into fragments containing all relevant T-cell epitopes. Cytokine-activated, allergen-pulsed neutrophils induced proliferative and cytokine responses of Bet v 1-specific T-cells irrespective of epitope specificity confirming that they fully processed and presented the allergen. HLA-DR-positive neutrophils were detected in cutaneous allergic LPR.ConclusionNeutrophils may serve as APC for local allergen-specific effector T-cells in allergic LPR.

Teaser

Neutrophils may serve as antigen-presenting cells in the allergic late-phase reaction.


https://ift.tt/2lhuPBc