A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse.
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.
Shen
HuaHao H
HH
Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, S. C. Johnson Medical Research Center, Scottsdale, AZ 85259, USA.
Ochkur
Sergei I
SI
McGarry
Michael P
MP
Crosby
Jeffrey R
JR
Hines
Edie M
EM
Borchers
Michael T
MT
Wang
Huiying
H
Biechelle
Travis L
TL
O'Neill
Katie R
KR
Ansay
Tracy L
TL
Colbert
Dana C
DC
Cormier
Stephania A
SA
Justice
J Paul
JP
Lee
Nancy A
NA
Lee
James J
JJ
D019264:Adoptive Transfer; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology* / Q000637:transplantation; D015848:Interleukin-5 / Q000172:deficiency / Q000235:genetics; D007442:Intubation, Intratracheal; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000336:Aerosols; D000485:Allergens; D015848:Interleukin-5; D010047:Ovalbumin