Long-lived reciprocal regulation of antigen-specific IgE and IgG2a responses in mice treated with glutaraldehyde-polymerized ovalbumin.

Previously, we discovered that administration of high Mr glutaraldehyde-polymerized ovalbumin (OA) to C57BL/6 mice prior to immunization with OA in A1(OH)3 adjuvant resulted in induction of an interferon-gamma (IFN-gamma) dependent, split tolerance in which maximal OA-specific IgE responses were 1-3% of those observed in saline-treated OA-[A1(OH)3] immunized controls. Concomitantly, these mice exhibited up to 10(3)-fold increases in OA-specific IgG2a synthesis. In this report we examine the longevity and resilience of these reciprocal effects on IgE inhibition/IgG2a enhancement over extended periods of time and following multiple re-exposures to the sensitizing allergen. The data indicate that the T-cell mediated changes in responsiveness which are induced upon exposure to glutaraldehyde-modified protein allergen, but not unmodified allergen, are (i) extremely long-lived (greater than 350 days); (ii) resistant to at least five re-immunizations with OA in A1(OH)3 adjuvant; and (iii) antigen-specific. The results are consistent with a virtually permanent shift in the OA-specific T-cell repertoire in vivo from one dominated by Th2-like patterns of cytokine synthesis (IL-4) to one dominated by Th1-like (IFN-gamma) cytokine production.