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.