INHIBITION OF T-CELL COSTIMULATION ABROGATES AIRWAY HYPERRESPONSIVENESS IN A MURINE MODEL

Activation of naive T cells requires at least two signals. In addition to the web characterized interaction of the T cell antigen receptor w ith the antigen/MHC expressed on an antigen-presenting cell, T cell ac tivation also requires costimulation by a second set of signals. The b est characterized costimulatory receptor is CD28, which binds to a fam ily of B7 ligands expressed on antigen-presenting cells. In asthma, al though activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bro nchial hyperresponsiveness had not been characterized. Therefore, we t ested the hypothesis that inhibition of the CD28:B7 costimulatory path way would abrogate airway hyperresponsiveness. Our results show that b lockade of costimulation with CTLA4-Ig, a fusion protein known to prev ent costimulation by blocking CD28:B7 interactions, inhibits airway hy perresponsiveness, inflammatory infiltration, expansion of thoracic ly mphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma.