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Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression.

Authors: Campbell, JD  Buckland, KF  McMillan, SJ  Kearley, J  Oldfield, WL  Stern, LJ  Gronlund, H  Van Hage, M  Reynolds, CJ  Boyton, RJ  Cobbold, SP  Kay, AB  Altmann, DM  Lloyd, CM  Larche, M 
Citation: Campbell JD, etal., J Exp Med. 2009 Jul 6;206(7):1535-47. Epub 2009 Jun 15.
Pubmed: (View Article at PubMed) PMID:19528258
DOI: Full-text: DOI:10.1084/jem.20082901

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.

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CRRD Object Information
CRRD ID: 4144196
Created: 2010-10-12
Species: All species
Last Modified: 2010-10-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.