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 cyt okine production to later Ag challenges. Although the mechanism of this aer osol-induced IgE tolerance is not completely understood, it may prevent sen sitization to inhaled Ags, which could otherwise lead to allergy and asthma . We examined the consequences of ongoing Th1 and Th2 responses in the lung s of mice during OVA inhalation to mimic conditions that may subvert tolera nce and lead to sensitization. We found that concurrent, secondary Th2 lung responses to keyhole limpet hemocyanin or primary responses to Nippostrong ylus larvae or Asperigillus fumagatus extract prevented establishment of Ig E tolerance to aerosolized OVA. Intranasal rIL-4 given before OVA aerosoliz ation also prevented establishment of tolerance, whereas concurrent Th1 res ponses to influenza virus or Mycobacterium bovis bacillus Calmette-Guerin h ad no effect. However, once established, aerosol tolerance to OVA could not be completely broken by OVA rechallenge concurrent with a secondary Th2 re sponse to keyhole limpet hemocyanin or A. fumagatus extract, or by intranas al rIL-4. These data suggest that the immune status of the lung of an indiv idual may profoundly influence the initial response to inhaled Ag, and that aerosol-induced IgE tolerance may not be appropriately established in indi viduals undergoing concurrent, Th2-mediated responses to Ags or pathogens.