Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression Academic Article uri icon

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abstract

  • 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.

authors

  • Campbell, John D
  • Buckland, Karen F
  • McMillan, Sarah J
  • Kearley, Jennifer
  • Oldfield, William LG
  • Stern, Lawrence J
  • Grönlund, Hans
  • van Hage, Marianne
  • Reynolds, Catherine J
  • Boyton, Rosemary J
  • Cobbold, Stephen P
  • Kay, A Barry
  • Altmann, Daniel M
  • Lloyd, Clare M
  • Larche, Mark

publication date

  • July 6, 2009

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