Cutting edge: B and T lymphocyte attenuator and programmed death receptor-1 inhibitory receptors are required for termination of acute allergic airway inflammation.
T cell activation is regulated by coordinate interaction of the T cell Ag receptor and costimulatory signals. Although there is considerable insight into processes that regulate the initiation of inflammation, less is known about the signals that terminate immune responses. We have examined the role of the inhibitory receptors programmed death receptor-1 and B and T lymphocyte attenuator in the regulation of allergic airway inflammation. Our results demonstrate that there is a temporally regulated expression of both the receptors and their ligands during the course of allergic airway inflammation. Following a single inhaled challenge, sensitized wild-type mice exhibit peak inflammation on day 3, which resolves by day 10. In contrast, mice deficient in the expression of programmed death receptor-1 or B and T lymphocyte attenuator have persistent inflammation out to 15 days following challenge. Thus, these receptors are critical determinants of the duration of allergic airway inflammation.
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Christine
C
Deppong
Twyla I
TI
Juehne
Michelle
M
Hurchla
Lindzy D
LD
Friend
Dulari D
DD
Shah
Christine M
CM
Rose
Traci L
TL
Bricker
Laurie P
LP
Shornick
Erika C
EC
Crouch
Theresa L
TL
Murphy
Michael J
MJ
Holtzman
Kenneth M
KM
Murphy
Jonathan M
JM
Green
D000208:Acute Disease; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C488868:BTLA protein, mouse; D008024:Ligands; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic