title: Role of IL-4 receptor α-positive CD4(+) T cells in chronic airway hyperresponsiveness.
abstract: TH2 cells and their cytokines are associated with allergic asthma in human subjects and with mouse models of allergic airway disease. IL-4 signaling through the IL-4 receptor α (IL-4Rα) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Rα-responsive CD4(+) T cells are critical for the induction of allergic asthma. However, mechanisms regulating acute and chronic allergen-specific TH2 responses in vivo remain incompletely understood.
  
  
  
  This study defines the requirements for IL-4Rα-responsive CD4(+) T cells and the IL-4Rα ligands IL-4 and IL-13 in the development of allergen-specific TH2 responses during the onset and chronic phase of experimental allergic airway disease.
  
  
  
  Development of acute and chronic ovalbumin (OVA)-induced allergic asthma was assessed weekly in CD4(+) T cell-specific IL-4Rα-deficient BALB/c mice (Lck(cre)IL-4Rα(-/lox)) and respective control mice in the presence or absence of IL-4 or IL-13.
  
  
  
  During acute allergic airway disease, IL-4 deficiency did not prevent the onset of TH2 immune responses and OVA-induced airway hyperresponsiveness or goblet cell hyperplasia, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. In contrast, deficiency of IL-13 prevented allergic asthma, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. Importantly, chronic allergic inflammation and airway hyperresponsiveness were dependent on IL-4Rα-responsive CD4(+) T cells. Deficiency in IL-4Rα-responsive CD4(+) T cells resulted in increased numbers of IL-17-producing T cells and, consequently, increased airway neutrophilia.
  
  
  
  IL-4-responsive T helper cells are dispensable for acute OVA-induced airway disease but crucial in maintaining chronic asthmatic pathology.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB) and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town, South Africa.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirstein
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB) and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town, South Africa.
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Nieuwenhuizen
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB) and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town, South Africa.
authors.forename: Jaisubash
authors.initials: J
authors.lastname: Jayakumar
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB) and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town, South Africa.
authors.forename: William G C
authors.initials: WGC
authors.lastname: Horsnell
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB) and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town, South Africa. Electronic address: frank.brombacher@icgeb.org.
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007958:Leukocyte Count; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D053662:Interleukin-4 Receptor alpha Subunit; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: IL-13; IL-4; T(H)2 cell; acute allergic airway disease; chronic asthma; cytokine receptors; gene-deficient mice