title: Bystander immunotherapy as a strategy to control allergen-driven airway inflammation.
abstract: Allergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), lung infiltration of Th2 cells, and high levels of IgE. To date, allergen-specific immunotherapy (SIT) is the only treatment that effectively alleviates clinical symptoms and has a long-term effect after termination. Unfortunately, SIT is unsuitable for plurisensitized patients, and highly immunogenic allergens cannot be used. To overcome these hurdles, we sought to induce regulatory CD4(+) T cells (Treg) specific to an exogenous antigen that could be later activated as needed in vivo to control allergic responses. We have established an experimental approach in which mice tolerized to ovalbumin (OVA) were sensitized to the Leishmania homolog of receptors for activated c kinase (LACK) antigen, and subsequently challenged with aerosols of LACK alone or LACK and OVA together. Upon OVA administration, AHR and allergic airway responses were strongly reduced. OVA-induced suppression was mediated by CD25(+) Treg, required CTLA-4 and ICOS signaling and resulted in decreased numbers of migrating airway dendritic cells leading to a strong impairment in the proliferation of allergen-specific Th2 cells. Therefore, inducing Treg specific to a therapeutic antigen that could be further activated in vivo may represent a safe and novel curative approach for allergic asthma.
authors.affiliation: IPMC, CNRS UMR7275, INSERM U1080 Université de Nice-Sophia Antipolis, Valbonne, France.
authors.forename: S
authors.initials: S
authors.lastname: Navarro
authors.affiliation: IPMC, CNRS UMR7275, INSERM U1080 Université de Nice-Sophia Antipolis, Valbonne, France.
authors.forename: A
authors.initials: A
authors.lastname: Lazzari
authors.affiliation: Institut Pasteur de Lille, INSERM U1011, Université de Lille 2, Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Kanda
authors.affiliation: Institut Pasteur de Lille, INSERM U1011, Université de Lille 2, Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Fleury
authors.affiliation: Institut Pasteur de Lille, INSERM U1011, Université de Lille 2, Lille, France.
authors.forename: D
authors.initials: D
authors.lastname: Dombrowicz
authors.affiliation: IPMC, CNRS UMR7275, INSERM U1080 Université de Nice-Sophia Antipolis, Valbonne, France.
authors.forename: N
authors.initials: N
authors.lastname: Glaichenhaus
authors.affiliation: IPMC, CNRS UMR7275, INSERM U1080 Université de Nice-Sophia Antipolis, Valbonne, France.
authors.forename: V
authors.initials: V
authors.lastname: Julia
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D060908:CTLA-4 Antigen / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000953:Antigens, Protozoan; D060908:CTLA-4 Antigen; D060889:Inducible T-Cell Co-Stimulator Protein; D053645:Interleukin-2 Receptor alpha Subunit; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania; D007073:Immunoglobulin E; D010047:Ovalbumin