T cells that are drawn to the airways by leukotrienes attack lung tissue and contribute to transplant rejection, according to Medoff and colleagues on page 97. Mice lacking the leukotriene receptor BLT1 were protected from lethal T cell attack. The authors thus suggest that drugs designed to block this receptor may have therapeutic potential in patients who develop a lethal complication of lung transplant called obliterative bronchiolitis.
Medoff and colleagues now show that BLT1-deficient mice were less likely to develop T cell-mediated airway obstruction following allogeneic tracheal transplantation, demonstrating that leukotriene-induced T cell migration contributes to disease. This finding is consistent with previous studies showing that inhibition of BLT1 signaling was protective in other mouse models of allogeneic transplantation. However the contribution of T cell trafficking was never evaluated in those models.
Elimination of BLT1 did not completely reverse T cell infiltration into the lung, suggesting that LTB4 does not act alone. The authors suggest that chemokines may also contribute to the T cell recruitment—a possibility they are currently investigating.