T cell-derived antigen binding molecules play a role in the induction of airway hyperresponsiveness.
We previously demonstrated that tracheal hyperreactivity (in vitro) and altered lung functions (in vivo) were induced during a delayed-type hypersensitivity (DTH) reaction in murine lungs. These alterations were transferable with T cells, suggesting that this animal model could be used as a model for cellular IgE-independent immunity. In the present study we demonstrated that depletion of T suppressor/cytotoxic cells failed to abolish the ability of transferred cells to induce hyperresponsiveness. Depletion of T helper cells partially inhibited the induction of hyperreactivity. Depletion of 14-30+ cells (the monoclonal antibody 14-30 reacts with a common isotype of T cell-derived antigen binding molecules [TABM] that can arm mast cells) completely abolished the ability to transfer hyperreactivity. The cromoglycate-like antiasthmatic drug nedocromil, which stabilizes mast cells, inhibited the induction of T cell-mediated hyperresponsiveness. Moreover, in mast cell-deficient mice, T cell-mediated hyperresponsiveness can be less induced compared with normal littermates. These experiments indicate that mast cells play at least a partial role in the induction of airway hyperresponsiveness in this model. Dexamethasone, a well-known inhibitor of phospholipase A2, inhibited the T cell-mediated hyperresponsiveness, whereas the cyclooxygenase inhibitor suprofen did not. This indicated that arachidonic acid metabolites, but not cyclooxygenase products, play a role in the induction of T cell-mediated hyperreactivity. Pretreatment with the lipoxygenase inhibitor AA-861 significantly inhibited the induction of tracheal hyperreactivity. Platelet-activating factor appeared not to be involved in the induction of hyperresponsiveness in this model, because the platelet-activating factor antagonist WEB 2170 failed to abolish the induction of T cell-mediated hyperreactivity. Intravenous injection of purified mast cell-arming TABM, followed by intranasal hapten challenge 30 min later, resulted in increased vascular permeability 2 h after challenge, which is characteristic of the early initiating phase of DTH. In addition, tracheal hyperreactivity (in vitro) and altered lung functions (in vivo) were observed 2 h after challenge. From these data we conclude that airway hyperreactivity and altered lung functions are induced by early steps in the cellular cascade of DTH.
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
J
J
Garssen
F P
FP
Nijkamp
E
E
Van Vugt
H
H
Van der Vliet
H
H
Van Loveren
D000403:Airway Resistance / Q000187:drug effects / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D007116:Immunization, Passive / Q000379:methods; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014132:Trachea / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D014611:Vaccination / Q000379:methods
D011948:Receptors, Antigen, T-Cell; D010853:Picryl Chloride