Down-regulation of immune responses to inhaled antigen: studies on the mechanism of induced suppression

Abstract

Repeated exposure of rats to an aerosol of ovalbumin (OVA) or its dinitrophenylated derivative (DNP-OVA) induced carrier-specific tolerance to subsequent challenge with the same haptenated antigen. Following parenteral challenge with DNP-OVA, both anti-DNP and anti-OVA IgE titres were reduced relative to controls, whereas anti-DNP responses following challenge with DNP-Ascaris were normal. Stimulation of tolerant rats with OVA, together with the polyclonal B-cell mitogen LPS, restored their capacity to respond to the antigen. In contrast to WAG rats, which have previously been shown to develop equivalent tolerance in the IgE an IgG antibody classes (Sedgwick & Holt, 1984), BN rats exposed to an OVA aerosol developed high serum titres of anti-OVA IgG. Following parenteral challenge with DNP-OVA, however, anti-DNP IgG responses in the BNs were markedly reduced relative to unexposed controls, while anti-OVA IgG titres were maintained at a high level. Further strain-dependent differences in T-cell function in tolerized rats appeared in in vivo assays of DTH reactivity and in in vitro antigen-driven lymphocyte proliferation. Both BN and WAG rats displayed diminished in vitro responses, whereas DTH reactions were only suppressed in the latter strain.