title: Immunosuppression in early postnatal days induces persistent and allergen-specific immune tolerance to asthma in adult mice.
abstract: Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma.
authors: Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China.
authors: Yan
authors: Y
authors: Chen
authors: Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China.
authors: Jin
authors: J
authors: Zhang
authors: Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China.
authors: Yong
authors: Y
authors: Lu
authors: Department of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China.
authors: Libo
authors: L
authors: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000166:cytology; D060908:CTLA-4 Antigen / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D003888:Desensitization, Immunologic; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007108:Immune Tolerance; D056724:Immunity, Humoral; D007073:Immunoglobulin E / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000485:Allergens; D060908:CTLA-4 Antigen; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D007073:Immunoglobulin E; D010047:Ovalbumin