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

Allergic sensitization in asthma develops as a consequence of complex inter actions between T cells and antigen-presenting cells. We have developed sev eral in vivo models to study allergen-specific T cell and B cell function a nd their relevance to allergic airway hyperresponsiveness (AHR), focusing o n 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 IgG(1), 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 t he BAL fluid of sensitized mice, suggesting impaired Th2 function in anti-C D86-treated animals. This effect was not seen when mice received treatment only before allergen challenge, indicating that anti-CD86 acts through inhi bition 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 a llergen-challenged mice. Further, this study demonstrates that T-B cell int eractions during allergic sensitization are amenable to therapeutic manipul ation and that selective blockade of accessory signals can be an effective means for modulating distinct T cell functions.