Am. J. Respir. Crit. Care Med., Vol 150, No. 6, Dec 1994, 1528-1538.
T cell-derived antigen binding molecules play a role in the induction of airway hyperresponsiveness
J Garssen, FP Nijkamp, E Van Vugt, H Van der Vliet and H Van Loveren
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
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.
