Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia.
The pathogenesis of asthma remains unclear. An in vivo murine model of antigen-induced airway hyperreactivity and inflammation was developed to investigate the possibility, suggested by a wealth of descriptive human data, that alterations in immunoregulation are important in the genesis of airway hyperreactivity. A/J mice developed airway hyperreactivity and markedly increased numbers of pulmonary inflammatory cells following intraperitoneal sensitization and intratracheal challenge with sheep red blood cells. Notably, eosinophils were a prominent component of the inflammatory infiltrate. The dependence of these phenomena, both pathologic and functional, on CD4+ T lymphocytes was investigated by in vivo depletion of CD4+ cells using the anti-CD4 mAb GK1.5. When administered before antigen challenge, GK1.5 completely prevented both airway hyperreactivity and the infiltration of eosinophils. This model provides the first direct demonstration of the dependence of airway hyperreactivity upon CD4+ T lymphocytes, and the results are consistent with the possibility that eosinophils are effectors of this response.
Gavett
S H
SH
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
Chen
X
X
Finkelman
F
F
Wills-Karp
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D012129:Respiratory Function Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D000109:Acetylcholine