| House dust mite sublingual immunotherapy: the role for transforming growth factor-beta and functional regulatory T cells. | |
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MedLine Citation:
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PMID: 19696440 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Sublingual allergen-specific immunotherapy is gaining popularity for treatment of allergic diseases, but underlying immunological mechanisms are unresolved. OBJECTIVES: To perform detailed immunological investigation of sublingual house dust mite (HDM) immunotherapy. METHODS: A 12-month randomized double-blind placebo-controlled study of sublingual HDM immunotherapy in 30 HDM-allergic subjects was performed, with 1-year open extension in 9 patients on active treatment. HDM-stimulated blood mononuclear cells were analyzed for proliferation, cytokines, and regulatory T cells (Tregs) by flow cytometry and ELISA. Effects of blocking transforming growth factor (TGF)-beta and IL-10 on proliferation were determined. Treg suppressor function and allergen-specific antibody levels were measured. Clinical efficacy was assessed by symptom, medication, and Juniper quality-of-life scores. MEASUREMENTS AND MAIN RESULTS: Allergen-induced CD4(+) T-cell division and IL-5 production were significantly decreased after 6- and 12-months' active treatment but not placebo. sTGF-betaRII blocked immunotherapy-induced suppression of allergen-specific T-cell proliferation, maximal at 6 months. Decreased allergen-specific CD4(+) T-cell proliferation and increased IL-10 secretion and serum Der p 2-specific IgG(4) were maximal at 24 months' active treatment. Treg (CD4(+)CD25(+)CD127(lo)/Foxp3(+)) function was demonstrated by suppression of allergen-specific effector T-cell (CD4(+)CD25(-)CD127(hi)) proliferation and cytokine production. Clinical efficacy of immunotherapy was supported by significantly decreased rhinitis symptom score, total asthma score, and Juniper quality-of-life score. CONCLUSIONS: This study establishes the novel finding that TGF-beta mediates the immunological suppression seen early in clinically effective sublingual HDM immunotherapy in addition to an increase in Tregs with suppressor function. Clinical trial registered with www.clinicaltrials.gov (NCT00250263). |
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Authors:
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Robyn E O'Hehir; Leanne M Gardner; Maria P de Leon; Belinda J Hales; Mark Biondo; Jo A Douglass; Jennifer M Rolland; Alessandra Sandrini |
Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2009-08-20 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 180 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-11-09 Completed Date: 2009-11-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 936-47 Citation Subset: AIM; IM |
Affiliation:
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Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Commercial Road, Melbourne, VIC 3004, Australia. robyn.ohehir@med.monash.edu.au |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00250263 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Sublingual Adolescent Adult Aged Allergens / administration & dosage Animals Asthma / therapy Double-Blind Method Female Humans Immunotherapy / methods* Interleukin-5 / biosynthesis Male Middle Aged Pyroglyphidae / immunology* Respiratory Hypersensitivity / therapy* Rhinitis, Allergic, Perennial / therapy T-Lymphocytes, Regulatory / immunology* Transforming Growth Factor beta / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Allergens; 0/Interleukin-5; 0/Transforming Growth Factor beta |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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