title: Cumulative exposure to CD8+ granzyme Bhi 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 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.
authors.affiliation: Emory Transplant Center, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mohammed
authors.forename: O
authors.initials: O
authors.lastname: Ulukpo
authors.forename: E C
authors.initials: EC
authors.lastname: Lawrence
authors.forename: F
authors.initials: F
authors.lastname: Fernandez
authors.forename: A
authors.initials: A
authors.lastname: Pickens
authors.forename: A A
authors.initials: AA
authors.lastname: Gal
authors.forename: S D
authors.initials: SD
authors.lastname: Force
authors.forename: K C
authors.initials: KC
authors.lastname: Easley
authors.forename: C P
authors.initials: CP
authors.lastname: Larsen
authors.forename: A D
authors.initials: AD
authors.lastname: Kirk
authors.forename: D C
authors.initials: DC
authors.lastname: Neujahr
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D001999:Bronchoscopy; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume; D005845:Georgia; D006084:Graft Rejection / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D053804:Granzymes / Q000097:blood / Q000378:metabolism*; D006801:Humans; D016018:Least-Squares Analysis; D008168:Lung / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013147:Spirometry; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C509213:GZMB protein, human; D053804:Granzymes