Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma

Frontiers in Immunology

Christine Happle¹  Jelena Skuljec¹  Anika Habener¹  Gesine Hansen¹  Hinrich Abken³  Markus Chmielewski³  Mandy Busse⁴ 

[1] Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany;Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;Clinic I Internal Medicine, University Hospital Cologne, Cologne, Germany;Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany;

关键词: allergic asthma;    chimeric antigen receptor;    regulatory T cells;    adoptive cell therapy;    ovalbumin mouse model;   

DOI  :  10.3389/fimmu.2017.01125

来源: DOAJ

【 摘 要 】

Cellular therapy with chimeric antigen receptor (CAR)-redirected cytotoxic T cells has shown impressive efficacy in the treatment of hematologic malignancies. We explored a regulatory T cell (Treg)-based therapy in the treatment of allergic airway inflammation, a model for asthma, which is characterized by an airway hyper-reactivity (AHR) and a chronic, T helper-2 (Th2) cell-dominated immune response to allergen. To restore the immune balance in the lung, we redirected Tregs by a CAR toward lung epithelia in mice upon experimentally induced allergic asthma, closely mimicking the clinical situation. Adoptively transferred CAR Tregs accumulated in the lung and in tracheobronchial lymph nodes, reduced AHR and diminished eosinophilic airway inflammation, indicated by lower cell numbers in the bronchoalveolar lavage fluid and decreased cell infiltrates in the lung. CAR Treg cells furthermore prevented excessive pulmonary mucus production as well as increase in allergen-specific IgE and Th2 cytokine levels in exposed animals. CAR Tregs were more efficient in controlling asthma than non-modified Tregs, indicating the pivotal role of specific Treg cell activation in the affected organ. Data demonstrate that lung targeting CAR Treg cells ameliorate key features of experimental airway inflammation, paving the way for cell therapy of severe allergic asthma.

【 授权许可】

Unknown