Sublingual immunotherapy induces IL-10–producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation

Background The immunologic mechanisms underlying sublingual immunotherapy (SLIT) are still unclear, particularly the role of regulatory T cells. Objective We sought to characterize allergen-specific T-cell responses during successful birch pollen SLIT. Methods Proliferation of PBMCs and PBMCs deplet...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2007-09, Vol.120 (3), p.707-713
Main Authors: Bohle, Barbara, PhD, Kinaciyan, Tamar, MD, Gerstmayr, Marianne, MSc, Radakovics, Astrid, Jahn-Schmid, Beatrice, PhD, Ebner, Christof, MD
Format: Article
Language:English
Subjects:
Administration, Sublingual
Allergens - administration & dosage
Allergens - immunology
Allergies
Allergy and Immunology
Bet v 1
Betula - immunology
Biological and medical sciences
Cell Proliferation
Cytokines
Desensitization, Immunologic
Dust
Enzyme-Linked Immunosorbent Assay
Flow cytometry
Forkhead Transcription Factors - biosynthesis
Forkhead Transcription Factors - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Hypersensitivity - prevention & control
IL-10
immune deviation
Immune system
Immune Tolerance
Immunopathology
Interferon-gamma - biosynthesis
Interferon-gamma - immunology
Interleukin-10 - biosynthesis
Interleukin-10 - immunology
Interleukin-4 - biosynthesis
Interleukin-4 - immunology
Investigations
Longitudinal Studies
Lymphocytes
Malus
Medical sciences
Pollen - immunology
regulatory T cells
RNA, Messenger - analysis
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Specific immunotherapy
sublingual immunotherapy
T cell receptors
T-cell tolerance
T-Lymphocytes, Regulatory - immunology
Tetanus
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Summary:Background The immunologic mechanisms underlying sublingual immunotherapy (SLIT) are still unclear, particularly the role of regulatory T cells. Objective We sought to characterize allergen-specific T-cell responses during successful birch pollen SLIT. Methods Proliferation of PBMCs and PBMCs depleted of CD25+ cells obtained from 9 patients before, after 4 weeks, and after 52 weeks of SLIT was assessed in response to the major birch pollen allergen Bet v 1, the homologous apple allergen Mal d 1, or tetanus toxoid. Allergen-induced cytokine responses and FoxP3 expression of T cells were analyzed by using real-time PCR. The role of IL-10 for regulatory activity of T cells was investigated. Results After 4 weeks, higher frequencies of circulating CD4+ CD25+ T cells were detected together with increased FoxP3 and IL-10 and reduced IL-4 and IFN-γ mRNA expression levels compared with those before SLIT. Proliferation to all 3 antigens was markedly reduced but increased significantly after depletion of CD25+ cells or addition of anti–IL-10 antibodies. After 52 weeks, proliferation in response to Mal d 1 or tetanus toxoid returned to pre-SLIT levels, whereas Bet v 1–induced proliferation remained significantly suppressed and was enhanced by neither depletion of CD25+ cells nor addition of anti–IL-10 antibodies. In parallel, increased IFN-γ and reduced IL-4, IL-10, and FoxP3 mRNA expression was detected. Neither TGF-β levels nor cell-cell contact–mediated suppression of CD4+ CD25+ cells changed during the course of SLIT. Conclusion SLIT induces regulatory T-cell suppression through IL-10 during the early phase and specific nonreactivity and immune deviation of allergen-specific T cells during the later phase of therapy. Clinical implications SLIT induces immune mechanisms comparable with subcutaneous specific immunotherapy.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2007.06.013