Correlation between eosinophilia induced by CD4(+) T cells and bronchial hyper-responsiveness.
The relationship between CD4(+) T cell-mediated airway eosinophilic inflammation and bronchial hyper-responsiveness (BHR) was investigated. Ovalbumin-reactive T(h)0 clones were adoptively transferred to unprimed BALB/c mice and then the mice were challenged by inhalation of the relevant antigen. Upon antigen provocation, infused T(h) clones infiltrated into the airways, followed by the accumulation and degranulation of eosinophils, goblet cell hyperplasia, edema and increase in bronchial responsiveness to acetylcholine. Transfer of several clones that differed in the levels of IL-5 production revealed that the magnitude of in vivo eosinophilia strongly correlated with the IL-5-producing capacity of the infused T(h) clones. Administration of anti-IL-5 mAb almost completely suppressed antigen-induced eosinophilic inflammation and BHR. Administration of anti-IL-4 mAb or anti-IFN-gamma mAb enhanced the eosinophilia and BHR, whereas anti-IL-2 mAb did not affect them. The number of accumulated eosinophils significantly correlated with the intensity of BHR. Our present results clearly demonstrated that CD4(+) T cells induced BHR as a result of eosinophilic inflammation. IL-5 totally regulated both responses.
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
A
A
Nakata
O
O
Kaminuma
K
K
Ogawa
H
H
Fujimura
K
K
Fushimi
H
H
Kikkawa
K
K
Naito
K
K
Ikezawa
R W
RW
Egan
A
A
Mori
D000109:Acetylcholine; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001982:Bronchial Diseases / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D016207:Cytokines / Q000378:metabolism; D047209:Eosinophil Peroxidase; D004802:Eosinophilia / Q000276:immunology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010544:Peroxidases / Q000032:analysis; D011657:Pulmonary Eosinophilia / Q000276:immunology; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D000109:Acetylcholine