human langerhans cells control th cells via programmed death-ligand 1 in response to bacterial stimuli and nickel-induced contact allergy人类的朗格汉斯细胞控制th细胞通过编程death-ligand 1针对细菌刺激和nickel-induced接触过敏.pdfVIP

Human Langerhans Cells Control Th Cells via Programmed Death-Ligand 1 in Response to Bacterial Stimuli and Nickel-Induced Contact Allergy 1 2 3 3 4 1 Manuel Hitzler , Otto Majdic , Guido Heine , Margitta Worm , Grit Ebert , Andreas Luch , Matthias Peiser1* 1 German Federal Institute for Risk Assessment (BfR), Department of Product Safety, Berlin, Germany, 2 Institute for Immunology, Medical University, Vienna, Austria, ´ ´ 3 Department of Dermatology and Allergy, Allergy-Center-Charite, CCM, Charite-University Medicine Berlin, Berlin, Germany, 4 Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany Abstract Langerhans cells (LCs) are suspected to initiate inflammatory immune responses to contact allergens and pathogenic bacteria. In chronic infectious diseases, programmed death ligand (PD-L) 1 exhibits both inhibitory and costimulatory functions on T cell-mediated activation and tolerance. Here, we investigated the effects of contact allergens and bacterial stimuli on PD-L1 expression in LCs and the effects of altered PD-L1 expression on cytokine release of subsequently cocultured T cells. Monocyte-derived LCs (MoLCs), LCs, and skin sections of patients suffering from allergic contact dermatitis were challenged with nickel and then analyzed for PD-L1 expression by confocal laser scanning microscopy and flow cytometry. In blocking experiments, we found that the release of Th cell specific cytokines was dependent on both stimulation of