title: Antigen-fixed leukocytes tolerize Th2 responses in mouse models of allergy.
abstract: Allergic diseases, including asthma and food allergies, are an increasing health concern. Immunotherapy is an effective therapeutic approach for many allergic diseases but requires long dose escalation periods and has a high risk of adverse reactions, particularly in food allergy. New methods to safely induce Ag-specific tolerance could improve the clinical approach to allergic disease. We hypothesized that Ag-specific tolerance induced by the i.v. injection of Ags attached to the surface of syngeneic splenic leukocytes (Ag-coupled splenocytes [Ag-SPs]) with the chemical cross-linking agent ethylene-carbodiimide, which effectively modulate Th1/Th17 diseases, may also safely and efficiently induce tolerance in Th2-mediated mouse models of allergic asthma and food allergy. Mice were tolerized with Ag-SP before or after initiation of OVA/alum-induced allergic airway inflammation or peanut-induced food allergy. The effects on disease pathology and Th2-directed cytokine and Ab responses were studied. Ag-SP tolerance prevented disease development in both models and safely tolerized T cell responses in an Ag-specific manner in presensitized animals. Prophylactically, Ag-SP efficiently decreased local and systemic Th2 responses, eosinophilia, and Ag-specific IgE. Interestingly, Ag-SP induced Th2 tolerance was found to be partially dependent on the function of CD25(+) regulatory T cells in the food allergy model, but was regulatory T cell independent in the model of allergic airway inflammation. We demonstrate that Ag-SP tolerance can be rapidly, safely, and efficiently induced in murine models of allergic disease, highlighting a potential new Ag-specific tolerance immunotherapy for Th2-associated allergic diseases.
authors: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Charles B
authors: CB
authors: Smarr
authors: Chia-Lin
authors: CL
authors: Hsu
authors: Adam J
authors: AJ
authors: Byrne
authors: Stephen D
authors: SD
authors: Miller
authors: Paul J
authors: PJ
authors: Bryce
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D010367:Arachis / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D021183:Peanut Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000485:Allergens; D010047:Ovalbumin