Development of allergic inflammation in a murine model of asthma is dependent on the costimulatory receptor OX40.
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.
Jember
A G
AG
Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Zuberi
R
R
Liu
F T
FT
Croft
M
M
D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology*
D000485:Allergens; D015848:Interleukin-5; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin