Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice

Gerard F. Hoyne, Robyn E. O’hehir, David C. Wraith, Wayne R. Thomas, Jonathan R. Lamb

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310 Citations (Scopus)

Abstract

Antigen-specific CD4+ T cells play an important role in the allergic immune response to house dust mite (HDM) allergens in humans. The group 1 allergen ofDermatophagoides spp. is a major target antigen in both B and T cell recognition of HDM. In vitro studies have shown that the presentation of peptides to human T cells under appropriate conditions may lead to a state of specific nonresponsiveness. Therefore, to determine ifpeptides are able to modulate the function of allergen-reactive T cells in vivo, we have used a murine model of T cell recognition of the HDM allergen Der p 1. The results demonstrate that inhalation of low concentrations ofpeptide containing the major T cell epitope of Der p 1 (residues 111-139), induces tolerance in naive C57BL/6J mice such that they become profoundly unresponsive to an immunogenic challenge with the intact allergen. When restimuhted in vitro with antigen, lymph node T calls isolated from tolerant mice secrete very low levels of interleukin 2, proliferate poorly, and are unable to provide cognate help to stimulate specific antibody production. Furthermore, intranasal peptide therapy was able to inhibit an ongoing immune response to the allergen in mice and this has potential implications in the development of allergen-based immunotherapy.

Original languageEnglish
Pages (from-to)1783-1788
Number of pages6
JournalJournal of Experimental Medicine
Volume178
Issue number5
DOIs
Publication statusPublished - 1 Nov 1993
Externally publishedYes

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