BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation

نویسندگان

  • Benjamin D. Medoff
  • Edward Seung
  • John C. Wain
  • Terry K. Means
  • Gabriele S.V. Campanella
  • Sabina A. Islam
  • Seddon Y. Thomas
  • Leo C. Ginns
  • Nir Grabie
  • Andrew H. Lichtman
  • Andrew M. Tager
  • Andrew D. Luster
چکیده

Leukotriene B4 is a lipid mediator that recently has been shown to have potent chemotactic activity for effector T lymphocytes mediated through its receptor, BLT1. Here, we developed a novel murine model of acute lung rejection to demonstrate that BLT1 controls effector CD8+ T cell trafficking into the lung and that disruption of BLT1 signaling in CD8+ T cells reduces lung inflammation and mortality in the model. In addition, we used BLT1-deficient mice and a BLT1 antagonist in two tracheal transplant models of lung transplantation to demonstrate the importance of BLT1 for the recruitment of T cells into tracheal allografts. We also show that BLT1-mediated CD8+ T cell recruitment plays an important role in the development of airway fibroproliferation and obliteration. Finally, in human studies of lung transplant recipients, we found that BLT1 is up-regulated on T lymphocytes isolated from the airways of patients with obliterative bronchiolitis. These data demonstrate that BLT1 contributes to the development of lung rejection and obliterative bronchiolitis by mediating effector T lymphocyte trafficking into the lung. This is the first report that describes a pathologic role for BLT1-mediated T lymphocyte recruitment in disease and identifies BLT1 as a potential therapeutic target after lung transplantation.

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عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 202  شماره 

صفحات  -

تاریخ انتشار 2005