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

Journal article

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, J; Buckland, K; McMillan, S; Kearley, J; Oldfield, W

• Publication status: Published
• Journal: Journal of experimental medicine
• Volume: 206
• Issue: 7
• Pages: 1535-1547
• Publication date: 2009-07-01
• DOI: 10.1084/jem.20082901
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: HLA-DR1 Antigen; Cats; Mice, Inbred C57BL; Lung; Receptors, Interleukin-10; Double-Blind Method; Peptides; Placebos; Allergens; Desensitization, Immunologic; Mice, Transgenic; Asthma; Bronchial Hyperreactivity; Forkhead Transcription Factors; Th2 Cells; Transforming Growth Factor beta; Interleukin-10; Glycoproteins; Randomized Controlled Trials as Topic; Epitopes; Animals; Humans; Immune Tolerance; Genes, MHC Class II; Mice; Disease Models, Animal