HLA-G on peripheral blood CD4+ T lymphocytes: a potential predictor for acute renal rejection

Abstract

Summary HLA‐G Expression in grafts and serum has been shown to improve graft acceptance. However, its expression on peripheral blood lymphocytes (PBLs) during acute rejection (AR) remains unknown. In this study, we serially monitored HLA‐G expression on CD4+ and CD8+ PBLs of 66 recipients undergoing renal transplantation using flow cytometry at different time points before and after transplantation, as well as during AR episode. In stable recipients, HLA‐G expression on CD4+ PBLs declined during the first week after transplantation and increased continuously with immunosuppressive therapy. Then, expression declined gradually after 1 month and remained at a higher level compared with pretransplantation. When AR occurred, HLA‐G expression decreased significantly compared with the stable level. In three recipients suffering from recurrent rejection, it remained at a low level despite impact immunosuppressive treatment. With mix lymphocyte assay, HLA‐G+ CD4+ T cells showed inhibitory role on proliferation of peripheral blood mononuclear cell. HLA‐G expression on CD8+ PBLs was almost undetectable at different time points in the recipients and healthy controls. Our results suggest that HLA‐G on CD4+ PBLs might provide a potential marker for the early diagnosis of renal AR and for the immunosuppressive status of recipients.

Immunological biomarkers of tolerance in human kidney transplantation: An updated literature review

“…It was shown that HLA‐G + CD4 + T cells and the expression level of HLA‐G on CD4 + T cells were significantly decreased after acute rejection. It is worthwhile to note that when acute rejection occurred, HLA‐G levels decreased compared with before and during the follow‐up phase after acute rejection (N. Lu et al, ). Other study reported that high‐level sHLA‐G after transplantation was independently related to graft acceptance.…”

“…Kidney graft is immediately damaged by the immune response during graft rejection, which is considered as the major cause of graft loss (J. Lu & Zhang, 2016;N. Lu et al, 2011).…”

Changes in HLA-G Expression by Leucocyte Subsets Following Renal Transplantation and the Effect of Immunosuppressive Drugs on Leucocyte HLA-G Expression in Vitro

“…Previous work has shown a significant increase in proportions of HLA-G+ CD4+ T cells post-renal transplantation in patients with stable graft function [39]. Furthermore, these cells were able to suppress a mixed lymphocyte reaction, indicative of a contribution to graft survival [40]. HLA-G expressed by dendritic cells or in soluble form can downregulate CD4 and CD8 on allostimulated T cells, leading to generation of suppressor function [41].…”

HLA-G Expressing Immune Cells in Immune Mediated Diseases

“…In the context of kidney transplants, it has been reported that HLA-G expression on T cells increases after the transplant, but significantly decreases in subjects experiencing an acute rejection. This data suggests that HLA-G might be involved in the protection of transplants against rejection and the levels of HLA-G on CD4+ may represent a potential marker in predicting episodes of renal rejection after kidney transplantation ( 58 , 59 ).…”