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 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.
Krinzman
S J
SJ
Pulmonary Division, Massachusetts General Hospital, Boston, USA.
De Sanctis
G T
GT
Cernadas
M
M
Mark
D
D
Wang
Y
Y
Listman
J
J
Kobzik
L
L
Donovan
C
C
Nassr
K
K
Katona
I
I
Christiani
D C
DC
Perkins
D L
DL
Finn
P W
PW
D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D018893:Bronchoalveolar Lavage; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006651:Histocytochemistry; D006967:Hypersensitivity / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D016085:Bronchoconstrictor Agents; D018106:CD28 Antigens; D007074:Immunoglobulin G; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin