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.
Hayglass
K T
KT
MRC Group for Allergy Research, Department of Immunology, University of Manitoba, Winnipeg, Canada.
Gieni
R S
RS
Stefura
W P
WP
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005976:Glutaral; D007108:Immune Tolerance / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000939:Epitopes; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D007073:Immunoglobulin E; D010047:Ovalbumin; D005976:Glutaral