Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model. |
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Authors: | S J Krinzman G T De Sanctis M Cernadas D Mark Y Wang J Listman L Kobzik C Donovan K Nassr I Katona D C Christiani D L Perkins P W Finn |
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Affiliation: | Pulmonary Division, Massachusetts General Hospital, Boston, USA. |
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Abstract: | Activation of naive T cells requires at least two signals. In addition to the well characterized interaction of the T cell antigen receptor with the antigen/MHC expressed on an antigen-presenting cell, T cell activation also requires costimulation by a second set of signals. The best characterized costimulatory receptor is CD28, which binds to a family of B7 ligands expressed on antigen-presenting cells. In asthma, although activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bronchial hyperresponsiveness had not been characterized. Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory pathway would abrogate airway hyperresponsiveness. Our results show that blockade of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness, inflammatory infiltration, expansion of thoracic lymphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma. |
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