Increased expression of graft intraepithelial T-cell pro-inflammatory cytokines compared with native lung during episodes of acute rejection

Abstract

<h4>Background</h4>We have previously reported that T-cell pro-inflammatory cytokines in the airways are associated with acute lung transplant rejection. However, during acute rejection episodes, we found no significant differences in airway intraepithelial T cell pro-inflammatory cytokines from stable and rejecting patients due to broad cytokine variability between patient groups. To overcome this limitation, we hypothesized that there would be an increase in pro-inflammatory intraepithelial T-cells in the graft compared with native airway during acute rejection.<h4>Methods</h4>Bronchial brushings from patients with stable graft function, evidence of acute rejection, bronchiolitis obliterans syndrome, infection, and healthy controls were stimulated and pro-inflammatory cytokines in intraepithelial T cells from graft and native airway were determined using multiparameter flow cytometry.<h4>Results</h4>There was a significant increase in intraepithelial T-cell interferon-γ and tumor necrosis factor (TNF)-α in the graft of patients with acute rejection compared with intraepithelial T cells obtained from the native airway, but no changes were noted among other patient groups. The increase in intraepithelial T-cell TNF-α was more pronounced the higher the acute rejection grade.<h4>Conclusions</h4>The graft airway epithelium is enriched with T cells producing interferon-γ and TNF-α during acute graft rejection. Therapeutic targeting of these pro-inflammatory cytokines and improved monitoring using this assay may reduce acute lung transplant rejection.