Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression
| العنوان: | Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression |
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| المؤلفون: | Clare M. Lloyd, A. Barry Kay, Stephen P. Cobbold, Sarah J. McMillan, William L. G. Oldfield, Hans Grönlund, Daniel M. Altmann, Marianne van Hage, Mark Larché, Jennifer Kearley, Catherine J. Reynolds, John D. Campbell, Rosemary J. Boyton, Lawrence J. Stern, Karen F. Buckland |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Allergy, medicine.medical_treatment, Genes, MHC Class II, Immunology, Mice, Transgenic, Article, Epitope, Immune tolerance, Placebos, Allergic sensitization, Epitopes, Mice, 03 medical and health sciences, Th2 Cells, 0302 clinical medicine, Double-Blind Method, Transforming Growth Factor beta, Fel d 1, Immune Tolerance, medicine, Animals, Humans, Immunology and Allergy, Receptors, Interleukin-10, Lung, Glycoproteins, Randomized Controlled Trials as Topic, 030304 developmental biology, 0303 health sciences, biology, HLA-DR1 Antigen, Interleukin, Forkhead Transcription Factors, Immunotherapy, Allergens, medicine.disease, Asthma, Interleukin-10, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, Interleukin 10, Desensitization, Immunologic, Cats, biology.protein, Bronchial Hyperreactivity, Peptides, 030215 immunology |
| الوصف: | 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. |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a61113aeeece48fc706c38a0453c48c8Test https://doi.org/10.1084/jem.20082901Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a61113aeeece48fc706c38a0453c48c8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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