title: Cellular and molecular mechanisms of IL-5 synthesis in atopic diseases: a study with allergen-specific human helper T cells.
abstract: BACKGROUND
  Cytokines produced by helper T cells are intimately involved in chronic allergic diseases associated with eosinophilic inflammation.
  
  
  OBJECTIVE
  We investigated the production of IL-5, a potent growth factor and chemotactic factor for eosinophils, by CD4+ T lymphocytes in patients with asthma.
  
  
  METHODS
  Allergen-specific T cell clones and T cell hybridomas were established from the peripheral blood lymphocytes of patients with asthma, and the responses to various stimuli were determined.
  
  
  RESULTS
  After nonspecific stimulation, IL-5 production by CD4+ T cells from both atopic and nonatopic subjects with asthma was significantly enhanced compared with that by cells from healthy controls. Peripheral blood mononuclear cells from atopic asthma patients both proliferated and produced IL-5 after incubation with mite allergen, suggesting that mite-specific helper T cells were involved in the eosinophilic inflammation of atopic asthma. A human IL-5 promoter/enhancer luciferase gene construct transfected into IL-5-producing T cell clones was clearly transcribed after stimulation, indicating that the 515 base pair IL-5 gene segment upstream of the coding region was sufficient to respond to activating signals in human helper T cells. The same gene segment was not transcribed in IL-5-nonproducing T cell clones, suggesting that human T cell IL-5 synthesis is regulated at the transcriptional level. Experiments with T cell hybridomas confirmed these findings and suggested that a unique transcription factor may be essential for human IL-5 gene transcription.
  
  
  CONCLUSIONS
  Enhanced IL-5 production by helper T cells seems to cause the eosinophilic inflammation of both atopic and nonatopic asthma. Elucidation of IL-5-specific regulatory mechanisms may facilitate the development of novel treatments for allergic diseases associated with eosinophilic inflammation.
authors.affiliation: Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mori
authors.forename: O
authors.initials: O
authors.lastname: Kaminuma
authors.forename: M
authors.initials: M
authors.lastname: Suko
authors.forename: T
authors.initials: T
authors.lastname: Mikami
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizaki
authors.forename: T
authors.initials: T
authors.lastname: Ohmura
authors.forename: A
authors.initials: A
authors.lastname: Hoshino
authors.forename: Y
authors.initials: Y
authors.lastname: Asakura
authors.forename: K
authors.initials: K
authors.lastname: Miyazawa
authors.forename: T
authors.initials: T
authors.lastname: Ando
authors.forename: Y
authors.initials: Y
authors.lastname: Okumura
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Okudaira
mesh_terms: D000328:Adult; D000818:Animals; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells; D006801:Humans; D006825:Hybridomas; D006967:Hypersensitivity / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008925:Mites / Q000276:immunology; D016133:Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D015848:Interleukin-5; D014157:Transcription Factors