Date of Award
Doctor of Philosophy
Polymerization of protein allergens with glutaraldehyde (GA) has been shown to lead to decreased local or systemic adverse reactions when used in human hyposensitization therapy. At the same time, clinical trials have revealed that their immunotherapeutic value was at least as good, and in many cases significantly better than that of the corresponding conventional native allergen extracts. Despite these advantages their mechanism of action remains unclear.;The purpose of this study was to determine the characteristics and classification of immunosuoppressive activity established as a consequence of treatment with GA-proteins.;Treatment of mice, a widely accepted animal prototype for human allergy, with GA-polymerized ovalbumin (OA-POL) led to highly efficient antigen-specific suppression of primary and secondary IgE responses. On the other hand, IgG antibody and delayed hypersensitivity responses were not suppressed. Decreased binding to antibodies against the native OA molecule occurred with all GA-modified OA preparations regardless of whether they were polymerized or not. On the other hand, the ability to suppress IgE responses appeared to correlate directly with the size of the polymers used. Suppression was transferable to syngeneic recipients and depended upon the presence in the donor spleens of live Thy 1.2+ and Lyt 1+ lymphocytes.;OA-POL treatment of mice previously immunized with OA (alum) abrogated ongoing IgE responses. Not only were IgE anti-OA responses 8-10 fold lower in the treated group, but anamnestic IgE responses were prevented. Abrogation persisted for over 300 days despite multiple OA (alum) boosters. These results, taken in combination with experiments demonstrating undiminished antigen- and IgE isotype-specific suppression more than seven months after a single course of OA-POL pretreatment, suggested the existence of memory suppressor T cells. Direct evidence for such cells was obtained in adoptive transfer experiments where memory Ts cells were shown to be long-lived ((GREATERTHEQ) 200 d), rapidly recallable and displaying greater suppressive activity than conventional "primary" suppressor cells.;The study suggests that homeostasis of IgE responses may be maintained, at least in part, by long-lived and boosterable antigen-specific, isotype-selective suppressor T cells. The experimental manipulation of such cells indicates that increasing their activity may provide a useful approach for the selective regulation of IgE- mediated hypersensitivity.
Hayglass, Kent Taylor, "Induction Of Antigen-specific, Isotype-selective Suppression Of Immunoglobulin-e Responses With Glutaraldehyde - Polymerized Ovalbumin" (1983). Digitized Theses. 1300.