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(+) 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.