Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients

Clin Exp Immunol. 2021 Feb;203(2):315-328. doi: 10.1111/cei.13533. Epub 2020 Oct 29.

Abstract

Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+ CD154+ and CD8+ CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+ CD154+ T cells (P = 0·001) and a low percentage of CD8+ CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+ CD154+ (P = 0·001) and CD8+ CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+ CD154+ , CD8+ CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+ CD154+ and CD8+ CD154+ T cells in parallel with other transplant factors.

Keywords: CD154+ T cells; HLA; acute cellular rejection; cell-mediated immunity (CMI); immunosuppression; liver transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Ligand / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Flow Cytometry / methods
  • Graft Rejection / immunology*
  • HLA-DRB1 Chains / immunology*
  • Heart Transplantation / methods
  • Humans
  • Liver Transplantation / methods
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology*
  • Transplantation, Homologous / methods
  • Young Adult

Substances

  • Biomarkers
  • HLA-DRB1 Chains
  • CD40 Ligand