Lung T-Cell Profile Alterations are Associated with Bronchiolitis Obliterans Syndrome in Cystic Fibrosis Lung Transplant Recipients

Lung. 2020 Feb;198(1):157-161. doi: 10.1007/s00408-019-00298-1. Epub 2019 Dec 5.

Abstract

The contribution of T-cells after lung transplant (LTx) remains controversial with no current consensus of their role concerning chronic lung allograft dysfunction. Using flow cytometry to assess T-cell subsets of bronchoalveolar lavage fluid (BALF) in 16 cystic fibrosis (CF) LTx recipients, we identified a decline in CD4+ T-cell frequency and an increase in CD8+ T-cell frequency in patients who developed severe bronchiolitis obliterans syndrome (BOS) (N = 10) when comparing baseline (6 months post-LTx) and follow-up (most recent bronchoscopy-clinical or surveillance per protocol). Comparing BOS to No BOS cohorts, significant differences were found in CD4+ T-cell frequency [17.4 (12.5, 28.2) vs 46.6 (44.4, 48.4), p = 0.003] and CD8+ T-cell frequency [65.6 (62.8, 75.3) vs 39.2 (32.2, 43.3), p = 0.014], respectively. The mean difference of the CD4:CD8 ratio was 0.87 units lower (95% CI - 1.44 to - 0.30, p = 0.006) than patients without BOS, while the median difference of the CD4:CD8 ratio was 0.92 units lower (95% CI - 1.83 to - 0.009, p = 0.048). Therefore, our results suggest that T-cell profiles measured through flow cytometry of BALF in the CF LTx population are associated with the development of severe BOS. Further work is needed in larger patient populations to validate our findings and to determine if this is useful for recipients who underwent LTx for other indications.

Keywords: Bronchiolitis obliterans syndrome; CD4; CD8; Chronic lung allograft dysfunction; Cystic fibrosis; Lung transplant; T-cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Bronchiolitis Obliterans / epidemiology
  • Bronchiolitis Obliterans / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • CD3 Complex / immunology
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Cystic Fibrosis / surgery*
  • Female
  • Graft Rejection / prevention & control
  • Humans
  • Immunophenotyping
  • Immunosuppressive Agents / therapeutic use
  • Lung Transplantation*
  • Male
  • Postoperative Complications / epidemiology
  • Postoperative Complications / immunology*
  • Severity of Illness Index
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / immunology*
  • Young Adult

Substances

  • CD3 Complex
  • Immunosuppressive Agents