A study of endothelial cell-lymphocyte responses in human renal transplantation.

Abstract

Histological studies have demonstrated vascular damage in all types of allograft rejection. It is likely that donor endothelium suffers the major and the first insult by the recipient's immune system since, in vivo, capillary endothelium expresses human lymphocyte antigen (HLA) class I and class II antigens. The present study was designed to examine whether injury to donor endothelial cells (ECs) by recipient peripheral blood mononuclear cells (PBMCs) can be demonstrated in vitro, and whether there is a relationship between the in vitro findings and the clinical outcome of renal allografts. Twenty renal transplant recipients were included in this study, and all patients were followed up for 6 months. PBMCs were isolated from the renal transplant recipients on three occasions; in the first 24-h post-transplantation, at the beginning of the second week, and in the third week post-transplantation. Additional samples were taken at the time of any acute rejection episode. These patients received renal allografts from 15 local cadaveric donors whose ECs were isolated. Donor-specific ECs and the corresponding renal transplant recipients' PBMCs and sera were employed in proliferation and cytotoxicity assays. Our results show that donor-specific ECs consistently induced a highly significant degree of recipient lymphocyte proliferative response (p < 0.05). However, no significant correlation between acute graft rejection and the degree of donor-specific EC-induced recipient lymphocyte proliferation was found. In contrast, there was a significant correlation between lymphocyte-induced EC cytolytic effects and acute renal graft rejection (p < 0.05). When conducted in larger studies, such information can have important implications in clinical transplantation.