The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness

Christian Taube, Nobuaki Miyahara, Vanessa Ott, Brad Swanson, Katsuyuki Takeda, Joan Loader, Leonard D. Shultz, Andrew M. Tager, Andrew D. Luster, Azzeddine Dakhama, Erwin W. Gelfand

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83 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3157-3164
Number of pages8
JournalJournal of Immunology
Volume176
Issue number5
DOIs
Publication statusPublished - Mar 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Taube, C., Miyahara, N., Ott, V., Swanson, B., Takeda, K., Loader, J., Shultz, L. D., Tager, A. M., Luster, A. D., Dakhama, A., & Gelfand, E. W. (2006). The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness. Journal of Immunology, 176(5), 3157-3164. https://doi.org/10.4049/jimmunol.176.5.3157