The role of coinhibitory pathways in allergen-specific CD4+ T cell responses

Abstract

Abstract More than 25% of the population suffers from IgE-mediated immune reactions and its related symptoms. T lymphocytes have a crucial role in initiating and promoting allergies and their responses are tightly regulated by numerous activating and inhibitory signals provided by APCs. Currently, there is limited knowledge regarding the role of inhibitory pathways in allergen-specific CD4+ T cell responses. To address this issue, patients allergic against house dust mites, birch pollen, mugwort pollen and grass pollen were recruited. PBMCs were isolated and then stimulated with allergenic extracts to evaluate coinhibitory pathways using blocking antibodies (e.g. nivolumab, ipilimumab) and to assess the expression of coinhibitory receptors on allergen-specific T cells. Allergenic extracts were analyzed for presence of TLR triggering molecules using NF-κB-eGFP reporter cells expressing TLR1/2, TLR2/6, TLR4 or TLR5. Furthermore, allergen-specific T cell reporters, T cell lines or T cell clones from allergic patients were cocultivated with engineered APCs that present allergenic peptides on MHC class II molecules and express different coinhibitory molecules. Blockade of the PD-1/PD-L1 axis strongly enhanced proliferation of allergen-specific CD4+ T cells in response to allergenic extracts. No correlation was found between IgE concentration and T cell proliferation. Preliminary results show a distinct expression pattern of coinhibitory molecules on allergen-specific T cells. In a next step Th1/Th2 cytokine patterns will be analyzed. Research was performed in accordance with the Declaration of Helsinki and approval of the local ethics committee was obtained (EK1538/2014).