Interleukin-4 is required for the induction of lung Th2 mucosal immunity

Am J Respir Cell Mol Biol. 1995 Jul;13(1):54-9. doi: 10.1165/ajrcmb.13.1.7598937.


Aerosol antigen challenge of ovalbumin-sensitized mice induced an eosinophilic airway inflammation that was dependent on interleukin (IL)-5 and CD4+, but not CD8+, T lymphocytes. The involvement of the Th2 phenotype of CD4+ T cells was supported by demonstrating that FACS-sorted purified lung T cells from sensitized, but not control, mice produced IL-4, IL-5, and IL-10 after activation of the CD3/TCR complex. To determine the role of IL-4 in this process, we used mice in which the gene for IL-4 was deleted by homologous recombination. Antigen challenge of IL-4 gene-targeted mice resulted in a marked attenuation of eosinophilic inflammation and IL-5 secretion. To more fully understand the time when IL-4 was involved, we administered a neutralizing anti-IL-4 antibody (11B11) either immediately before antigen challenge or during immunization. Inhibition of IL-4 before antigen challenge had little effect on antigen-induced eosinophil infiltration. However, when 11B11 was administered during immunization, there was a marked reduction in eosinophil infiltration. Cross-linking of the CD3/TCR complex of FACS-sorted lung T cells revealed that only when anti-IL-4 was administered during immunization was there an inhibition of T cell-derived IL-5 and IgE production. These results suggest that IL-4 is central both to the induction of a local Th2 response and to the development of eosinophilic inflammation of the lung. Moreover, we suggest a sequential involvement of IL-4 and IL-5, with IL-4 committing naive T cells to a Th2 phenotype which upon activation by aerosol provocation secrete IL-5, resulting in eosinophil accumulation.

MeSH terms

  • Animals
  • Cell Separation
  • Eosinophils / immunology
  • Flow Cytometry
  • Gene Deletion
  • Immunity, Cellular / immunology*
  • Inflammation / etiology
  • Inflammation / immunology
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism*
  • Lung / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mucous Membrane / immunology
  • Ovalbumin / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / cytology
  • Th2 Cells / immunology*


  • Interleukin-4
  • Ovalbumin