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

J Clin Invest. 1996 Dec 15;98(12):2693-9. doi: 10.1172/JCI119093.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Airway Resistance / physiology
  • Animals
  • Bronchoalveolar Lavage
  • Bronchoconstrictor Agents / pharmacology
  • CD28 Antigens / metabolism*
  • CD28 Antigens / pharmacology
  • Cell Division / drug effects
  • Disease Models, Animal
  • Flow Cytometry
  • Histocytochemistry
  • Hypersensitivity / metabolism
  • Immunoglobulin E / blood
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / pharmacology
  • Immunohistochemistry
  • Inflammation / metabolism
  • Lung / cytology
  • Lung / immunology
  • Lung / metabolism*
  • Male
  • Methacholine Chloride / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*


  • Bronchoconstrictor Agents
  • CD28 Antigens
  • Immunoglobulin G
  • Methacholine Chloride
  • Immunoglobulin E
  • Ovalbumin