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

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

doi:10.1172/JCI119093

Pulmonary Division, Massachusetts General Hospital, Boston, USA.

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Published in Volume 98, Issue 12 on December 15, 1996
J Clin Invest. 1996;98(12):2693–2699. https://doi.org/10.1172/JCI119093.
© 1996 The American Society for Clinical Investigation

Published December 15, 1996 - Version history

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

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, and P W Finn

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

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, and P W Finn

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