REGULATION OF ANTIGEN-SPECIFIC IGE, IGG1, AND MAST-CELL RESPONSES TO INGESTED ALLERGEN BY MUCOSAL TOLERANCE INDUCTION

Mucosal administration of soluble protein Ags results in profound immu nologic nonresponsiveness, characterized by reduced production of Th1 and Th2 cytokines and concomitant suppressed Ig production. It has bee n suggested that Th2 cells are required for the induction and maintena nce of this tolerogenic state. In this study, we show that oral tolera nce induction abrogates subsequent Th2-driven Ag-specific IgE and IgG1 . responses, while intranasal tolerance induction only blocks the prod uction of IgE, but not IgG1. Consistent with suppressed IgE serum leve rs, elevated IFN-gamma production was observed in the spleens of toler ized mice. Moreover, both oral and intranasal tolerance induction were found to inhibit intestinal mast cell responses upon subsequent primi ng and intragastric provocation. Transfer of total splenocytes or puri fied CD4(+), but not CD8(+) T cells from intranasally tolerized mice c learly suppressed ongoing Ag-specific IgE, but not IgG1, responses in primed recipients. In addition, coadministration of IFN-gamma-neutrali zing Abs completely blocked the transfer of suppression to primed reci pients. These results show that Th2 cells can be subjected to toleranc e induction, by inducing cross-regulatory, IFN-gamma-producing CD4(+) T cells. Moreover, our results point out differences in the regulation of T cell-dependent Ag-specific IgE and IgG1 responses.