Repeated aerosol allergen exposure suppresses inflammation in B-cell-deficient mice with established allergic asthma.
BACKGROUND
Repeated allergen administration is a well-established therapeutic strategy for desensitizing patients with allergic disease. Similarly, repeated inhalation of antigen by mice with established allergen-induced asthma suppresses allergic inflammation. The mechanisms underlying antigen-dependent suppression of allergic immune responses remain unknown. In previous studies, we found that repeated aerosol antigen challenges in sensitized mice reduced eosinophils while increasing plasma cells and antibody in the lungs. We sought to test whether plasma cells and antibody played a role in suppression of allergic disease.


METHODS
We primed wild-type and B-cell-deficient (microMT) mice with 25 microg ovalbumin (OVA) precipitated in alum on days 0 and 5, nebulized weekly with 1% OVA, 1 h, twice daily, for up to 6 weeks, and assessed lung inflammation, mucus hypersecretion, and IgE/IgG1.


RESULTS
Kinetic studies revealed that initial aerosol exposure induced high numbers of eosinophils, lymphocytes, and macrophages within lung infiltrates and increased mucus production in wild-type mice. After 3-4 weeks of antigen exposure, eosinophils diminished while lymphocytes, plasma cells, and macrophages and mucus hypersecretion increased. However, by 6 weeks, lung inflammation and mucus hypersecretion were dramatically reduced. In contrast, repeated aerosol challenges maintained OVA-specific IgG1 and IgE production. Repeated aerosol antigen challenges in microMT mice resulted in reduced lung inflammation and mucus hypersecretion and the development of smooth muscle hypertrophy of the pulmonary microvasculature.


CONCLUSIONS
B cells and antibody do not appear to play a role in antigen-dependent suppression of allergic responses in mice.
Jungsuwadee
Paiboon
P
Department of Dermatology, VIRCC, University of Vienna Medical School, Vienna, Austria.
Benkovszky
Michaela
M
Dekan
Gerhard
G
Stingl
Georg
G
Epstein
Michelle M
MM
D000336:Aerosols; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology
D000336:Aerosols; D000485:Allergens; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin