Modulation of inhaled antigen-induced IgE tolerance by ongoing Th2 responses in the lung.
The normal response to inhaled Ag is the absence of Ag-specific IgE and cytokine production to later Ag challenges. Although the mechanism of this aerosol-induced IgE tolerance is not completely understood, it may prevent sensitization to inhaled Ags, which could otherwise lead to allergy and asthma. We examined the consequences of ongoing Th1 and Th2 responses in the lungs of mice during OVA inhalation to mimic conditions that may subvert tolerance and lead to sensitization. We found that concurrent, secondary Th2 lung responses to keyhole limpet hemocyanin or primary responses to Nippostrongylus larvae or Asperigillus fumagatus extract prevented establishment of IgE tolerance to aerosolized OVA. Intranasal rIL-4 given before OVA aerosolization also prevented establishment of tolerance, whereas concurrent Th1 responses to influenza virus or Mycobacterium bovis bacillus Calmette-Guérin had no effect. However, once established, aerosol tolerance to OVA could not be completely broken by OVA rechallenge concurrent with a secondary Th2 response to keyhole limpet hemocyanin or A. fumagatus extract, or by intranasal rIL-4. These data suggest that the immune status of the lung of an individual may profoundly influence the initial response to inhaled Ag, and that aerosol-induced IgE tolerance may not be appropriately established in individuals undergoing concurrent, Th2-mediated responses to Ags or pathogens.
Hurst
S D
SD
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA. hurst@corgentech.com
Seymour
B W
BW
Muchamuel
T
T
Kurup
V P
VP
Coffman
R L
RL
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007156:Immunologic Memory; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000008:administration & dosage; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology / Q000469:parasitology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000336:Aerosols; D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin