Suppression of IgE responses in inbred rats by repeated respiratory tract exposure to antigen: responder phenotype influences isotype specificity of induced tolerance.

Abstract

Repeated exposure of rats to an aerosol of ovalbumin (OVA) induced tolerance to subsequent parenteral challenge with the same antigen. In the low-IgE responder WAG strain, responses in both the IgE and IgG classes were affected, whereas rats of the moderate (Lou/M) and high-IgE responder BN strain developed high titers of anti-OVA IgG in serum during exposure with concomitant tolerance in the IgE class. Repeated parenteral challenge, however, failed to elicit significant secondary anti-OVA IgG responses in the Lou/M and BN strains, suggesting that the isotype specificity of induced tolerance in these strains was not absolute. Spleen and respiratory tract lymph node cells, but not serum from aerosol-exposed BN rats, were capable of transferring IgE isotype- and antigen-specific tolerance. Dose response experiments demonstrated that the low-IgE responder WAG strain was exquisitely sensitive to tolerance induction in response to antigen inhalation, being susceptible to dosages in the nanogram range; at least 1000 times more antigen was required in the high-IgE responder BN to induce comparable tolerance in the IgE class. It was also apparent that the IgE isotype was more readily suppressed than the IgG isotype in both high- and low-IgE responder strains.