title: Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy.
abstract: 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) A(2) 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 PLA(2) 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 PLA(2) 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 PLA(2)-stimulated PBMCs (P<0.01) and IFN-gamma (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Allergy and Clinical Immunology, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Tarzi
authors.forename: S
authors.initials: S
authors.lastname: Klunker
authors.forename: C
authors.initials: C
authors.lastname: Texier
authors.forename: A
authors.initials: A
authors.lastname: Verhoef
authors.forename: S O
authors.initials: SO
authors.lastname: Stapel
authors.forename: C A
authors.initials: CA
authors.lastname: Akdis
authors.forename: B
authors.initials: B
authors.lastname: Maillere
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
authors.forename: M
authors.initials: M
authors.lastname: Larché
mesh_terms: D000328:Adult; D001514:Bee Venoms / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D016233:Immunotherapy, Active / Q000379:methods*; D007271:Injections, Intradermal; D016753:Interleukin-10 / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D010455:Peptides / Q000276:immunology; D010741:Phospholipases A / Q000008:administration & dosage* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D001514:Bee Venoms; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D018793:Interleukin-13; D010455:Peptides; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D016753:Interleukin-10; D010741:Phospholipases A