title: Inducible costimulator regulates Th2-mediated inflammation, but not Th2 differentiation, in a model of allergic airway disease.
abstract: A novel costimulatory molecule expressed on activated T cells, inducible costimulator (ICOS), and its ligand, B7-related protein-1 (B7RP-1), were recently identified. ICOS costimulation leads to the induction of Th2 cytokines without augmentation of IL-2 production, suggesting a role for ICOS in Th2 cell differentiation and expansion. In the present study, a soluble form of murine ICOS, ICOS-Ig, was used to block ICOS/B7RP-1 interactions in a Th2 model of allergic airway disease. In this model, mice are sensitized with inactivated Schistosoma mansoni eggs and are subsequently challenged with soluble S. mansoni egg Ag directly in the airways. Treatment of C57BL/6 mice with ICOS-Ig during sensitization and challenge attenuated airway inflammation, as demonstrated by a decrease in cellular infiltration into the lung tissue and airways, as well as by a decrease in local IL-5 production. These inhibitory effects were not due to a lack of T cell priming nor to a defect in Th2 differentiation. In addition, blockade of ICOS/B7RP-1 interactions during ex vivo restimulation of lung Th2 effector cells prevented cytokine production. Thus, blockade of ICOS signaling can significantly reduce airway inflammation without affecting Th2 differentiation in this model of allergic airway disease.
authors.affiliation: Committee on Immunology and Section of Pulmonary and Critical Care, Department of Medicine, and Ben May Institute for Cancer Research, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Tesciuba
authors.forename: S
authors.initials: S
authors.lastname: Subudhi
authors.forename: R P
authors.initials: RP
authors.lastname: Rother
authors.forename: S J
authors.initials: SJ
authors.lastname: Faas
authors.forename: A M
authors.initials: AM
authors.lastname: Frantz
authors.forename: D
authors.initials: D
authors.lastname: Elliot
authors.forename: J
authors.initials: J
authors.lastname: Weinstock
authors.forename: L A
authors.initials: LA
authors.lastname: Matis
authors.forename: J A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: A I
authors.initials: AI
authors.lastname: Sperling
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000947:Antigens, Helminth / Q000008:administration & dosage; D018122:B7-1 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D012550:Schistosoma mansoni / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000947:Antigens, Helminth; D018122:B7-1 Antigen; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; C556694:Icos protein, mouse; D007166:Immunosuppressive Agents; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007073:Immunoglobulin E