Role of IL-4 receptor α-positive CD4(+) T cells in chronic airway hyperresponsiveness

Frank Kirstein, Natalie E Nieuwenhuizen, Jaisubash Jayakumar, William G C Horsnell, Frank Brombacher

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


BACKGROUND: 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.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: IL-4-responsive T helper cells are dispensable for acute OVA-induced airway disease but crucial in maintaining chronic asthmatic pathology.

Original languageEnglish
Pages (from-to)1852-1862.e9
JournalJournal of Allergy and Clinical Immunology
Issue number6
Early online date11 Dec 2015
Publication statusPublished - Jun 2016


  • Animals
  • Asthma
  • CD4-Positive T-Lymphocytes
  • Chronic Disease
  • Cytokines
  • Disease Models, Animal
  • Female
  • Humans
  • Immunoglobulin E
  • Immunoglobulin G
  • Interleukin-4 Receptor alpha Subunit
  • Leukocyte Count
  • Mice
  • Mice, Knockout
  • Ovalbumin
  • Respiratory Hypersensitivity
  • T-Lymphocyte Subsets
  • Th2 Cells
  • Journal Article


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