title: Anti-CD86 (B7.2) treatment abolishes allergic airway hyperresponsiveness in mice.
abstract: Allergic sensitization in asthma develops as a consequence of complex interactions between T cells and antigen-presenting cells. We have developed several in vivo models to study allergen-specific T cell and B cell function and their relevance to allergic airway hyperresponsiveness (AHR), focusing on the role of the costimulatory molecules CD80 and CD86. Treatment of mice with anti-CD86, but not anti-CD80, significantly inhibited increased serum levels of ovalbumin (OA)-specific IgE and IgG1, airway eosinophilia, and AHR both after 10 d of OA aerosol exposure (in the absence of adjuvant) and after intraperitoneal sensitization followed by repeated airway challenges. Inhibition of AHR was associated with decreased IL-4 and IL-5 levels in the BAL fluid of sensitized mice, suggesting impaired Th2 function in anti-CD86-treated animals. This effect was not seen when mice received treatment only before allergen challenge, indicating that anti-CD86 acts through inhibition of allergic sensitization and not simply by inhibiting the influx of inflammatory cells. These data suggest that the CD86 costimulatory ligand plays a major role in the development of allergic inflammation and AHR in allergen-challenged mice. Further, this study demonstrates that T-B cell interactions during allergic sensitization are amenable to therapeutic manipulation and that selective blockade of accessory signals can be an effective means for modulating distinct T cell functions.
authors.affiliation: Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
authors.forename: A
authors.initials: A
authors.lastname: Haczku
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: I
authors.initials: I
authors.lastname: Redai
authors.forename: E
authors.initials: E
authors.lastname: Hamelmann
authors.forename: G
authors.initials: G
authors.lastname: Cieslewicz
authors.forename: A
authors.initials: A
authors.lastname: Joetham
authors.forename: J
authors.initials: J
authors.lastname: Loader
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Irvin
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000917:Antibody Formation / Q000187:drug effects; D015703:Antigens, CD / Q000276:immunology*; D051940:B7-2 Antigen; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D004558:Electric Stimulation; D004802:Eosinophilia / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000150:complications*; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008168:Lung / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000503:physiopathology; D010047:Ovalbumin / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D014132:Trachea / Q000503:physiopathology
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D007073:Immunoglobulin E; D010047:Ovalbumin