The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness.
Animals, Bronchial-Hyperreactivity, CD8-Positive-T-Lymphocytes, Interleukin-13, Leukotriene-B4, Mast-Cells, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Mice-Knockout, Mice-Transgenic, Receptors-Antigen-T-Cell, Receptors-IgE, Receptors-Leukotriene-B4, Receptors-Purinergic-P2
J Immunol 2006 Mar; 176(5):3157-64.
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.
Taube, C; Miyahara, N; Ott, V; Swanson, B; Takeda, K; Loader, J; Shultz, L D.; Tager, A M.; Luster, A D.; Dakhama, A; and Gelfand, E W., "The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness." (2006). Faculty Research 2000 - 2009. 1318.