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

HHH Shen, SI Ochkur, MP McGarry… - The Journal of …, 2003 - journals.aai.org
HHH Shen, SI Ochkur, MP McGarry, JR Crosby, EM Hines, MT Borchers, H Wang…
The Journal of Immunology, 2003journals.aai.org
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 …
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.
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