T cell-mediated airway hyperreactivity in mice.
Inadequate reactions of the immune system, i.e. allergic or hypersensitivity reactions, may lead to lung tissue injury and possibly airway hyperreactivity. In extrinsic asthma, mast cells are considered to play a pivotal role in inducing hyperreactivity by producing various mediators. Immunoglobulin E is a well-known inducer of mast cell mediator release, and is thus often considered important. Asthma induced by a small molecular moiety such as toluene diisocyanate (TDI) is only in 15% of patients associated with increased IgE levels. TDI is a known inducer of cellular immune responses. We are investigating the relationship of type IV hypersensitivity, as an example of IgE-independent cellular hypersensitivity, with the induction of airway hyperreactivity. We have studied mice which were sensitized with picryl chloride. After antigen challenge in such sensitized mice, peribronchial and perivascular accumulation of macrophages and lymphocytes was highest 48 h after challenge. Two hours after challenge and from 7 days onwards no infiltration was found. At several time points after challenge, changes in smooth muscle tone of mouse tracheas were measured isometrically. The response to carbachol increased from 2 h after challenge, reaching a maximum 48 h after challenge and lasted for at least 3 weeks. This hyperreactivity was not found in athymic (nude) mice. We conclude from these preliminary data that airway hyperreactivity can be immunologically induced other than by IgE, and that in this model it is not associated with the presence of a mononuclear infiltrate. These experimental data indicate a potential role for T cells in inducing airway hyperreactivity, a common denominator of patients suffering from asthma.
Van Loveren
H
H
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Garssen
J
J
Nijkamp
F P
FP
D000403:Airway Resistance / Q000276:immunology; D000818:Animals; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*