Cumulative exposure to CD8+ granzyme Bhi T cells is associated with reduced lung function early after lung transplantation

Transplant Proc. 2011 Dec;43(10):3892-8. doi: 10.1016/j.transproceed.2011.09.072.

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 Bhi 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 FEV1 slope. There was a negative correlation between 1-year exposure and FEV1 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 Bhi levels, granzyme Bhi 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Biomarkers / metabolism
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoscopy
  • CD8-Positive T-Lymphocytes / enzymology*
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Forced Expiratory Volume
  • Georgia
  • Graft Rejection / enzymology*
  • Graft Rejection / immunology
  • Graft Rejection / physiopathology
  • Granzymes / blood
  • Granzymes / metabolism*
  • Humans
  • Least-Squares Analysis
  • Lung / enzymology*
  • Lung / immunology
  • Lung / physiopathology
  • Lung Transplantation / adverse effects
  • Lung Transplantation / immunology*
  • Male
  • Middle Aged
  • Spirometry
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • GZMB protein, human
  • Granzymes