Asthma is thought to result from an abnormal expansion of CD4 T cells reactive with airborne
allergens, and pathology is controlled by several
cytokines of the T helper type 2 (Th2) family. The exact molecules which are involved in generating
allergen-reactive T cells are not clear. Studies with blocking
reagents or knockout animals have shown that the CD28/B7 interaction partially controls development of allergic
asthma in mouse models, but may not be the sole molecule involved. In this report, we have investigated the role of the
tumor necrosis factor receptor family member OX40 in allergic
inflammation using OX40-deficient mice. OX40 has been shown to participate in regulating clonal expansion and memory development of CD4 T cells and may synergize with CD28. Our studies demonstrate that OX40(-/)- mice, primed with the model
allergen ovalbumin and challenged through the airways with aerosolized
antigen, are severely impaired in their ability to generate a Th2 response characterized by high levels of
interleukin (IL)-5,
IL-4, and
immunoglobulin E. Moreover, OX40(-/)- mice exhibit diminished
lung inflammation, including an 80-90% reduction in
eosinophilia and mucus production, less goblet cell
hyperplasia, and significantly attenuated airway hyperreactivity. These studies highlight the potential importance of OX40 in development of allergic
asthma and suggest that targeting OX40 may prove useful therapeutically.