Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness.
Recent studies in both human and rodents have indicated that in addition to CD4+ T cells, CD8+ T cells play an important role in allergic inflammation. We previously demonstrated that allergen-sensitized and -challenged CD8-deficient (CD8-/-) mice develop significantly lower airway hyperresponsiveness (AHR), eosinophilic inflammation, and IL-13 levels in bronchoalveolar lavage fluid compared with wild-type mice, and that all these responses were restored by adoptive transfer of in vivo-primed CD8+ T cells or in vitro-generated effector CD8+ T cells (T(EFF)). Recently, leukotriene B4 and its high affinity receptor, BLT1, have been shown to mediate in vitro-generated T(EFF) recruitment into inflamed tissues. In this study we investigated whether BLT1 is essential for the development of CD8+ T cell-mediated allergic AHR and inflammation. Adoptive transfer of in vivo-primed BLT1+/+, but not BLT1-/-, CD8+ T cells into sensitized and challenged CD8-/- mice restored AHR, eosinophilic inflammation, and IL-13 levels. Moreover, when adoptively transferred into sensitized CD8-/- mice, in vitro-generated BLT1+/+, but not BLT1-/-, T(EFF) accumulated in the lung and mediated these altered airway responses to allergen challenge. These data are the first to show both a functional and an essential role for BLT1 in allergen-mediated CD8+ T(EFF) recruitment into the lung and development of AHR and airway inflammation.
Miyahara
Nobuaki
N
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Takeda
Katsuyuki
K
Miyahara
Satoko
S
Taube
Christian
C
Joetham
Anthony
A
Koya
Toshiyuki
T
Matsubara
Shigeki
S
Dakhama
Azzeddine
A
Tager
Andrew M
AM
Luster
Andrew D
AD
Gelfand
Erwin W
EW
D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments; D018102:Receptors, Leukotriene B4 / Q000378:metabolism*
D000485:Allergens; D016827:CD8 Antigens; D016207:Cytokines; D004527:Egg Proteins; C110366:OVA-8; D010446:Peptide Fragments; D018102:Receptors, Leukotriene B4; D010047:Ovalbumin