Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4558K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Campbell, J. D. Articles by Larché, M. Search for Related Content PubMed PubMed Citation Articles by Campbell, J. D. Articles by Larché, M. Social Bookmarking                            What's this?

¹ MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, ² Leukocyte Biology Section, ³ Lung Immunology Group, and ⁴ Allergy and Clinical Immunology, National Heart and Lung Institute and ⁵ Infectious Diseases Department, Investigative Sciences, Faculty of Medicine, Imperial College, London SW7 2 AZ, UK
⁶ University of Massachusetts Medical School, Worcester, MA 01655
⁷ Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet and University Hospital, Stockholm S-171 76, Sweden
⁸ Sir William Dunn School of Pathology, Oxford OX1 3RE, UK
⁹ Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario L8N 4A6, Canada

CORRESPONDENCE Clare M. Lloyd: c.lloyd{at}imperial.ac.uk

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other ("linked") epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10⁺ T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti–IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans.

Abbreviations used: AHR, airway hyperreactivity; BAL, bronchoalveolar lavage; i.d., intradermal(ly); i.n., intranasal(ly); PE, phycoerythrin.

© 2009 Campbell et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS