A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse

J Immunol. 2003 Mar 15;170(6):3296-305. doi: 10.4049/jimmunol.170.6.3296.

Abstract

Asthma and mouse models of allergic respiratory inflammation are invariably associated with a pulmonary eosinophilia; however, this association has remained correlative. In this report, a causative relationship between eosinophils and allergen-provoked pathologies was established using eosinophil adoptive transfer. Eosinophils were transferred directly into the lungs of either naive or OVA-treated IL-5(-/-) mice. This strategy resulted in a pulmonary eosinophilia equivalent to that observed in OVA-treated wild-type animals. A concomitant consequence of this eosinophil transfer was an increase in Th2 bronchoalveolar lavage cytokine levels and the restoration of intracellular epithelial mucus in OVA-treated IL-5(-/-) mice equivalent to OVA-treated wild-type levels. Moreover, the transfer also resulted in the development of airway hyperresponsiveness. These pulmonary changes did not occur when eosinophils were transferred into naive IL-5(-/-) mice, eliminating nonspecific consequences of the eosinophil transfer as a possible explanation. Significantly, administration of OVA-treated IL-5(-/-) mice with GK1.5 (anti-CD4) Abs abolished the increases in mucus accumulation and airway hyperresponsiveness following adoptive transfer of eosinophils. Thus, CD4(+) T cell-mediated inflammatory signals as well as signals derived from eosinophils are each necessary, yet alone insufficient, for the development of allergic pulmonary pathology. These data support an expanded view of T cell and eosinophil activities and suggest that eosinophil effector functions impinge directly on lung function.

MeSH terms

  • Adoptive Transfer
  • Aerosols
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Animals
  • Bronchial Hyperreactivity / genetics
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Eosinophils / immunology*
  • Eosinophils / pathology*
  • Eosinophils / transplantation
  • Interleukin-5 / deficiency
  • Interleukin-5 / genetics
  • Intubation, Intratracheal
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mucus / metabolism
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Pulmonary Eosinophilia / genetics
  • Pulmonary Eosinophilia / immunology
  • Pulmonary Eosinophilia / pathology
  • Respiratory Hypersensitivity / genetics
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / pathology*
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology

Substances

  • Aerosols
  • Allergens
  • Interleukin-5
  • Ovalbumin