T-CELL-DERIVED ANTIGEN-BINDING MOLECULES PLAY A ROLE IN THE INDUCTIONOF AIRWAY HYPERRESPONSIVENESS

We previously demonstrated that tracheal hyperreactivity (in vitro) an d altered lung functions (in vivo) were induced during a delayed-type hypersensitivity (DTH) reaction in murine lungs. These alterations wer e transferable with T cells, suggesting that this animal model could b e used as a model for cellular IgE-independent immunity. In the presen t study we demonstrated that depletion of T suppressor/cytotoxic cells failed to abolish the ability of transferred cells to induce hyperres ponsiveness. Depletion of T helper cells partially inhibited the induc tion of hyperreactivity. Depletion of 14-30(+) cells (the monoclonal a ntibody 14-30 reacts with a common isotype of T cell-derived antigen b inding molecules [TABM] that can arm mast cells) completely abolished the ability to transfer hyperreactivity. The cromoglycate-like antiast hmatic drug nedocromil, which stabilizes mast cells, inhibited the ind uction of T cell-mediated hyperresponsiveness. Moreover, in mast cell- deficient mice, T cell-mediated hyperresponsiveness can be less induce d compared with normal littermates. These experiments indicate that ma st cells play at least a partial role in the induction of airway hyper responsiveness in this model. Dexamethasone, a well-known inhibitor of phospholipase A(2), inhibited the T cell-mediated hyperresponsiveness , whereas the cyclooxygenase inhibitor suprofen did not. This indicate d that arachidonic acid metabolites, but not cyclooxygenase products, play a role in the induction of T cell-mediated hyperreactivity. Pretr eatment 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 i n this model, because the platelet-activating factor antagonist WEB 21 70 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 vascul ar permeability 2 h after challenge, which is characteristic of the ea rly initiating phase of DTH. In addition, tracheal hyperreactivity (in vitro) and altered lung functions (in vivo) were observed 2 h after c hallenge. From these data we conclude that airway hyperreactivity and altered lung functions are induced by early steps in the cellular casc ade of DTH.