Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy

• Published in: Clinical and experimental allergy Vol. 36; no. 4; pp. 465 - 474
• Main Authors: Tarzi, M., Klunker, S., Texier, C., Verhoef, A., Stapel, S. O., Akdis, C. A., Maillere, B., Kay, A. B., Larché, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2006; Blackwell; Wiley Subscription Services, Inc; Wiley
• Subjects: Adult; Allergic diseases; allergy; Apis mellifera; Bee Venoms; Bee Venoms - immunology; Biological and medical sciences; Cell Division; Cell Division - immunology; cytokine; Cytokines; Cytokines - immunology; Drug Hypersensitivity; Drug Hypersensitivity - genetics; Drug Hypersensitivity - immunology; Drug Hypersensitivity - therapy; epitope; Epitopes, T-Lymphocyte; Epitopes, T-Lymphocyte - immunology; Female; Forkhead Transcription Factors; Forkhead Transcription Factors - genetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; Gene Expression Regulation - immunology; HLA-DR Antigens; HLA-DR Antigens - immunology; human; Humans; Immunoglobulin G; Immunoglobulin G - immunology; Immunohistochemistry; Immunohistochemistry - methods; Immunopathology; immunotherapy; Immunotherapy, Active; Immunotherapy, Active - methods; Injections, Intradermal; Interleukin-10; Interleukin-10 - immunology; Interleukin-13; Interleukin-13 - immunology; Leukocytes, Mononuclear; Leukocytes, Mononuclear - immunology; Life Sciences; Male; Medical sciences; Microbiology and Parasitology; Peptides; Peptides - immunology; Phospholipases A; Phospholipases A - administration & dosage; Phospholipases A - immunology; Signal Transduction; Signal Transduction - genetics; Signal Transduction - immunology; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - immunology; T cells; tolerance/suppression/anergy; Transcription Factors; Transcription Factors - immunology; Treatment Outcome; Human; Immunopathology; Allergy; Anergy; Antigenic determinant; Peptides; transcription factors; Cytokine; Tolerance; Gene expression; Suppressor gene; T cells; Signal transduction; Immunology; Treatment; tolerance/suppression/ anergy; Immunotherapy; Interleukin 10; T-Lymphocyte; Transcription factor; epitope
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02469.x

Summary Background Allergen‐derived (T cell epitope) peptides may be safer for immunotherapy than native allergen, as they do not cross‐link immunoglobulin (Ig)E. However, HLA polymorphism results in multiple potential epitopes. Synthetic peptides of phospholipase (PL) A2 were selected for a peptide vaccine, on the basis of binding affinity for commonly expressed HLA‐DR molecules. Objective To evaluate treatment with an HLA‐DR‐based PLA2 peptide vaccine in subjects with mild honeybee allergy in an open, controlled study. Methods Twelve volunteers with allergy to bee venom received nine intradermal injections of PLA2 peptides, with six untreated subjects serving as controls. Outcome was assessed by the size of the late‐phase cutaneous reaction to allergen, peripheral blood mononuclear cell (PBMC) proliferation, cytokine release, and expression of genes associated with immune regulation. Results Subjects receiving peptides showed a decrease in the magnitude of the late‐phase cutaneous reaction to bee venom compared with controls (P=0.03). The proliferation of venom‐stimulated PBMCs decreased in treated subjects compared with controls (P=0.01). Peptide treatment reduced the production of IL‐13 by PLA2‐stimulated PBMCs (P<0.01) and IFN‐γ (P<0.01), and increased the production of IL‐10 (P=0.02). Transcription of the suppressor of cytokine signalling (Socs)3 gene was significantly increased following therapy. A transient, but modest, increase in allergen‐specific IgG was also observed. Conclusion HLA‐DR‐based T cell epitopes modify surrogate markers associated with successful immunotherapy and induction of immune regulation, supporting the concept that this form of treatment may be efficacious in human allergic disease.