Ectopic expression of IL-5 identifies an additional CD4(+) T cell mechanism of airway eosinophil recruitment.
CD4(+) T cells have a critical role in the development of allergic pulmonary inflammation, including the recruitment of eosinophils to the airway lumen and interstitium. The expression of interleukin (IL)-5 by CD4(+) cells has, in particular, often been lionized as the central link between allergic inflammation and the concomitant expansion or recruitment of eosinophils. The mechanism(s) by which CD4(+) T cells mediates eosinophil recruitment was assessed with gene knockout mice deficient for T cells or T cell subtypes and a unique IL-5 transgenic mouse (line NJ.1726) that constitutively overexpresses this cytokine in the lung epithelium. Pulmonary IL-5 expression is significantly attenuated in T cell- and CD4(+) but not CD8(+) cell-deficient animals, suggesting an obvious explanation for the lack of eosinophils in the lungs of T cell-deficient and CD4(-/-) mice. However, although the constitutive expression of IL-5 in the lung epithelium of NJ.1726 mice elicited an eosinophilia in the airway lumen of both naive and ovalbumin-treated mice, in the absence of CD4(+) cells, allergen-mediated eosinophil recruitment to the bronchoalveolar lavage fluid was abolished. Moreover, intranasal instillation of the potent eosinophil-specific chemokine eotaxin-2 was incapable of eliciting eosinophil recruitment in naive and ovalbumin-treated NJ.1726 CD4(-/-) mice, suggesting that eosinophil trafficking during allergic inflammatory responses is a consequence of a CD4(+) cell-mediated event(s) in addition to IL-5 expression and the establishment of a pulmonary chemokine gradient.
Crosby
Jeffrey R
JR
Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, USA.
Shen
H H
HH
Borchers
M T
MT
Justice
J P
JP
Ansay
T
T
Lee
J J
JJ
Lee
N A
NA
D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D054423:Chemokine CCL24; D019742:Chemokines, CC / Q000008:administration & dosage / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004848:Epithelium / Q000378:metabolism; D007114:Immunization; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000235:genetics; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology / Q000473:pathology
D000485:Allergens; C515485:Ccl24 protein, mouse; D054423:Chemokine CCL24; D019742:Chemokines, CC; D015848:Interleukin-5; D010047:Ovalbumin