Suppression of the anti-trimellityl (TM) IgE response in mice by conjugates of TM with polyvinyl alcohol

Abstract

The i.p. injection of 1 microgram of TM3-OA or TM9-OA with 1 mg of A1(OH)3 into B6D2F1 mice elicited the production of antibodies of the IgE and other classes to the trimellityl (TM) group and ovalbumin (OA). The induction of anti-TM antibodies belonging to the IgE and other immunoglobulin classes was specifically suppressed by the administration of tolerogenic conjugates prepared by coupling trimellitic anhydride (TMA) to the hydrophilic non-immunogenic polymer, polyvinyl alcohol (PVA), prior to immunization with TM-OA conjugates. More importantly, established anti-TM responses were also suppressed by these TM-PVA conjugates. By contrast, however, treatment with TM-PVA conjugates did not affect either the primary or the established anti-OA antibody response. The tolerogenic effects of the PVA conjugates were dose-dependent and appeared also to be dependent on the epitope density. Treatment with these conjugates also prevented immunized mice from showing any symptoms of systemic anaphylaxis on challenge with polyvalent TM-protein conjugates. These findings indicate that these conjugates may have the potential of useful therapeutic agents for the treatment of TMA-induced pulmonary hypersensitivity diseases.