The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness.
Studies in both humans and rodents have suggested that CD8+ T cells contribute to the development of airway hyperresponsiveness (AHR) and that leukotriene B4 (LTB4) is involved in the chemotaxis of effector CD8+ T cells (T(EFF)) to the lung by virtue of their expression of BLT1, the receptor for LTB4. In the present study, we used a mast cell-CD8-dependent model of AHR to further define the role of BLT1 in CD8+ T cell-mediated AHR. C57BL/6+/+ and CD8-deficient (CD8-/-) mice were passively sensitized with anti-OVA IgE and exposed to OVA via the airways. Following passive sensitization and allergen exposure, C57BL/6+/+ mice developed altered airway function, whereas passively sensitized and allergen-exposed CD8-/- mice failed to do so. CD8-/- mice reconstituted with CD8+ T(EFF) developed AHR in response to challenge. In contrast, CD8-/- mice reconstituted with BLT1-deficient effector CD8+ T cells did not develop AHR. The induction of increased airway responsiveness following transfer of CD8+ T(EFF) or in wild-type mice could be blocked by administration of an LTB4 receptor antagonist confirming the role of BLT1 in CD8+ T cell-mediated AHR. Together, these data define the important role for mast cells and the LTB4-BLT1 pathway in the development of CD8+ T cell-mediated allergic responses in the lung.
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Christian
C
Taube
Nobuaki
N
Miyahara
Vanessa
V
Ott
Brad
B
Swanson
Katsuyuki
K
Takeda
Joan
J
Loader
Leonard D
LD
Shultz
Andrew M
AM
Tager
Andrew D
AD
Luster
Azzeddine
A
Dakhama
Erwin W
EW
Gelfand
D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D005260:Female; D018793:Interleukin-13 / Q000502:physiology; D007975:Leukotriene B4 / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D017455:Receptors, IgE / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D018102:Receptors, Leukotriene B4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018793:Interleukin-13; C503704:Ltb4r1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D017455:Receptors, IgE; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D007975:Leukotriene B4