AEROSOL-INDUCED IMMUNOGLOBULIN (IG)-E UNRESPONSIVENESS TO OVALBUMIN DOES NOT REQUIRE CD8(-CELL RECEPTOR (TCR)-GAMMA() OR T)DELTA(+) T-CELLSOR INTERFERON (IFN)-GAMMA IN A MURINE MODEL OF ALLERGEN SENSITIZATION/

Mice exposed for 20 min daily to aerosolized ovalbumin (OVA) for 10 d at concentrations from 1 to 0.01% OVA made greatly reduced immunoglobu lin (Ig)-E responses to subsequent immunogenic OVA challenges, given e ither intraperitoneally or by aerosol. This IgE-specific unresponsiven ess lasted for at least four months. However, these aerosol-treated mi ce were primed for larger OVA-specific IgG1 and IgG2a responses. The s pecific reduction in IgE responses was not due to preferential inducti on of a T helper (Th)-1 response as aerosol OVA-primed mice made great ly reduced Th2 and no detectable Th1 response after rechallenge in vit ro. Consistent with this, the increase in circulating eosinophils obse rved in control Th2-primed mice was absent in aerosol OVA-treated anim als. Interferon (IFN)-gamma was not required for this unresponsiveness , as IFN-gamma knockout mice and anti-IFN-gamma antibody-treated wild- type mice had greatly reduced levels of IgE similar to wild-type contr ols. CD8(+) T cells played a relatively small role as IgE responses we re reduced to about the same extent in beta(2) microglobulin-deficient , or in anti-CD8-treated wild-type mice as in normal mice after aeroso l OVA treatment. Similarly, T cell receptor (TCR)-gamma/delta T cells were not required for maximal inhibition of the IgE response. These re sults demonstrate that exposure to inhaled protein antigens can induce a state of unresponsiveness of CD4(+) T cells that results in a prolo nged loss of IgE and eosinophil responses to subsequent challenges. Th is T cell unresponsiveness was shown not to require CD8(+) or TCR-gamm a/delta(+) T cells or IFN-gamma.