Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice

Angela Franciska Haczku, Katsuyuki Takeda, Imre Redai, Eckard Hamelmann, Gregory Cieslewicz, Anthony Joetham, Joan Loader, James J. Lee, Charles Irvin, Erwin W. Gelfand

Research output: Contribution to journalArticle

94 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1638-1643
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume159
Issue number5 I
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Haczku, A. F., Takeda, K., Redai, I., Hamelmann, E., Cieslewicz, G., Joetham, A., Loader, J., Lee, J. J., Irvin, C., & Gelfand, E. W. (1999). Anti-CD86 (B7.2) Treatment abolishes allergic airway hyperresponsiveness in mice. American Journal of Respiratory and Critical Care Medicine, 159(5 I), 1638-1643.