Cumulative Exposure to CD8+ Granzyme B hi T Cells Is Associated with Reduced Lung Function Early after Lung Transplantation

Abstract

Outcomes following lung transplant remain suboptimal. This is attributable to variable posttransplant recovery of lung function, and inconsistent degrees of lung function loss after peak function is reached. Granzyme B is elevated in the blood and bronchoalveolar lavage (BAL) in acute rejection. We hypothesized that persistent exposure to T cells high in granzyme B would negatively correlate with lung function. We investigated cumulative exposure measured as the area-under-the-curve (AUC) of CD8 + T cell granzyme B hi cells in the first year posttransplant in both BAL and blood in 24 transplant recipients. We assessed the correlation between cumulative 1-year exposure and FEV 1 slope. There was a negative correlation between 1-year exposure and FEV 1 slope within the first year ( r = −0.63; P = .001). This relationship persisted even when adjusted for transplant type, gender, age, rejection, and indication for transplantation. In contrast, no relationship was seen with the 1-year AUC and lung function after 1 year posttransplant. In contrast to the BAL granzyme B hi levels, granzyme B hi levels from the blood showed no relationship with lung function. These findings suggest that CD8 + T-cell–driven factors are responsible for early improvements in lung function after transplantation.