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

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.
(© 2020 British Society for Immunology.)