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Peptide immunothera...
Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression
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Campbell, JD (author)
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Buckland, KF (author)
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McMillan, SJ (author)
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Kearley, J (author)
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Oldfield, WLG (author)
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Stern, LJ (author)
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- Gronlund, H (author)
- Karolinska Institutet
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- van Hage, M (author)
- Karolinska Institutet
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Reynolds, CJ (author)
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Boyton, RJ (author)
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Cobbold, SP (author)
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Kay, AB (author)
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Altmann, DM (author)
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Lloyd, CM (author)
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Larche, M (author)
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(creator_code:org_t)
- 2009-06-15
- 2009
- English.
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 206:7, s. 1535-1547
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http://jem.rupress.o...
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https://doi.org/10.1...
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Abstract
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- 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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- art (subject category)
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- By the author/editor
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Campbell, JD
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Buckland, KF
-
McMillan, SJ
-
Kearley, J
-
Oldfield, WLG
-
Stern, LJ
-
show more...
-
Gronlund, H
-
van Hage, M
-
Reynolds, CJ
-
Boyton, RJ
-
Cobbold, SP
-
Kay, AB
-
Altmann, DM
-
Lloyd, CM
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Larche, M
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show less...
- Articles in the publication
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The Journal of e ...
- By the university
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Karolinska Institutet