The Leukotriene B4 Receptor (BLT1) Is Required for Effector CD8+ T Cell-Mediated, Mast Cell-Dependent Airway Hyperresponsiveness

Published on Mar 1, 2006in Journal of Immunology4.886
· DOI :10.4049/JIMMUNOL.176.5.3157
Christian Taube51
Estimated H-index: 51
Nobuaki Miyahara33
Estimated H-index: 33
+ 8 AuthorsErwin W. Gelfand113
Estimated H-index: 113
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 (TEFF) 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+ TEFF 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+ TEFF 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.
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