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. 1996 Dec 15;98(12):2693–2699. doi: 10.1172/JCI119093

Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model.

S J Krinzman 1, G T De Sanctis 1, M Cernadas 1, D Mark 1, Y Wang 1, J Listman 1, L Kobzik 1, C Donovan 1, K Nassr 1, I Katona 1, D C Christiani 1, D L Perkins 1, P W Finn 1
PMCID: PMC507732  PMID: 8981913

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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Selected References

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