T-cell-mediated induction of airway hyperreactivity in mice.
Airway hyperreactivity is an almost universal feature of asthma. The origin of this phenomenon is poorly understood. Although a role has been suggested for cell-mediated immune responses in the induction of bronchial hyperreactivity, direct evidence for such a role is not available. In the present study it was investigated whether delayed-type hypersensitivity (DTH) to picryl chloride (PCI) in mice used as a model for cellular immunity can induce airway hyperreactivity. DTH infiltrates in the lungs of PCI-sensitized and challenged BALB/c mice occurred at 24 h after challenge, and they were maximal at 48 h. The inflammatory infiltrate resolved gradually and disappeared completely after 14 days. Whether or not the DTH-like inflammatory reaction influenced lung function parameters was tested in vivo. From these experiments it was concluded that the pulmonary resistance in mice with a DTH-like inflammation was increased. Dynamic compliance was unchanged. In PCI-sensitized and challenged BALB/c mice, hyperreactivity of isolated trachea to carbachol was found at 2 h after challenge. It was maximal at 48 h after challenge and lasted for at least 3 wk. The response was antigen-specific. Moreover, the phenomenon was T-cell-dependent since in athymic (nude) mice no hyperreactivity to carbachol was detected. In addition, hyperreactivity could be observed after challenge of mice that were passively sensitized by intravenous injection of lymphoid cells from sensitized donor mice. After T-cell depletion of the donor lymphoid cells, the hyperreactivity to carbachol was significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Garssen
J
J
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Nijkamp
F P
FP
Van Der Vliet
H
H
Van Loveren
H
H
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D007111:Immunity, Cellular / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012129:Respiratory Function Tests; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*; D014132:Trachea / Q000276:immunology