Development of murine allergic asthma is dependent upon B7-2 costimulation

Andrea M. Keane-Myers, William C. Gause, Fred D. Finkelman, X. D. Xhou, Marsha Wills-Karp

Research output: Contribution to journalArticlepeer-review

Abstract

Allergic asthma is thought to be mediated by CD4+ T lymphocytes producing the Th2-associated cytokines, IL-4, and IL-5. Recently, the costimulatory molecules B7-1 and B7-2, which are expressed on the surface of APC, have been suggested to influence the development of Th1 vs Th2 immune responses. We examined the in vivo role of these costimulatory molecules in the pathogenesis of Th2-mediated allergen-induced airway hyperresponsiveness in a murine model of asthma. In this model, OVA-sensitized A/J mice develop significant increases in airway responsiveness, pulmonary eosinophilia, and pulmonary Th2 cytokine expression following aspiration challenge with OVA as compared with PBS-control animals. Strikingly, administration of anti-B7-2 mAb to OVA-treated mice abolished allergen-induced airway hyperresponsiveness, pulmonary eosinophilia, and elevations in serum IgG1 and IgE levels. Anti-B7-2 treatment of OVA-treated mice reduced both total lung IL-4 and IL-5 mRNA and bronchoalveolar lavage fluid IL-4 and IL-5 protein levels, with no significant changes in IFN-γ message or protein levels. In contrast, treatment with anti-B7-1 mAbs had no effect on allergen-induced airway hyperresponsiveness, IgE production, or cytokine production, however, it significantly suppressed pulmonary eosinophilia. We conclude that B7-2 provides the necessary costimulatory signal required for the development of in vivo allergic responses to inhaled allergen exposure.

Original languageEnglish (US)
Pages (from-to)1036-1043
Number of pages8
JournalJournal of Immunology
Volume160
Issue number2
StatePublished - Jan 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Development of murine allergic asthma is dependent upon B7-2 costimulation'. Together they form a unique fingerprint.

Cite this