Regulation of antigen-specific IgE, IgG1, and mast cell responses to ingested allergen by mucosal tolerance induction

Astrid G. Van Halteren, Maarten J. Van Der Cammen, Deborah Cooper, Huub F. Savelkoul, Georg Kraal, Patrick G. Holt

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

91 Citaten (Scopus)

Samenvatting

Mucosal administration of soluble protein Ags results in profound immunologic nonresponsiveness, characterized by reduced production of Th1 and Th2 cytokines and concomitant suppressed Ig production. It has been suggested that Th2 cells are required for the induction and maintenance of this tolerogenic state. In this study, we show that oral tolerance induction abrogates subsequent Th2-driven Ag-specific IgE and IgG1 responses, while intranasal tolerance induction only blocks the production of IgE, but not IgG1. Consistent with suppressed IgE serum levels, elevated IFN-γ production was observed in the spleens of tolerized mice. Moreover, both oral and intranasal tolerance induction were found to inhibit intestinal mast cell responses upon subsequent priming and intragastric provocation. Transfer of total splenocytes or purified CD4+, but not CD8+, T cells from intranasally tolerized mice clearly suppressed ongoing Ag-specific IgE, but not IgG1, responses in primed recipients. In addition, coadministration of IFN-γ-neutralizing Abs completely blocked the transfer of suppression to primed recipients. These results show that Th2 cells can be subjected to tolerance induction, by inducing cross-regulatory, IFN-γ-producing CD4+ T cells. Moreover, our results point out differences in the regulation of T cell-dependent Ag-specific IgE and IgG1 responses.

Originele taal-2Engels
Pagina's (van-tot)3009-3015
Aantal pagina's7
TijdschriftJournal of Immunology
Volume159
Nummer van het tijdschrift6
StatusGepubliceerd - 1997
Extern gepubliceerdJa

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