RESUMEN
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.
Asunto(s)
Endotelio Vascular/inmunología , Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Linfocitos/inmunología , Técnicas de Cocultivo , Citotoxicidad Inmunológica , Antígenos de Histocompatibilidad Clase II/análisis , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Interferón gamma/farmacología , Activación de Linfocitos , Donantes de TejidosRESUMEN
Portal-enteric (PE) transplantation of the pancreas allograft provides maintained physiologic drainage, and theoretically the portal delivery of transplantation antigens may have beneficial effects on the graft acceptance leading to improved graft survival. To determine whether the technique of pancreas placement affects the incidence of acute rejection we reviewed our experience in technically successful PE and systemic-bladder (SB) drained simultaneous pancreas and kidney (SPK) transplants performed between 1989 and 1994. Forty-seven recipients were included (SB = 30, PE = 17). All patients received cyclosporine based quadruple immunosuppression and survived at least 1 month. The two groups were comparable in HLA mismatches, cold ischemia time and level of immunosuppression at time of rejection. In the SB group the incidence of rejection was 1.04 kidney rejection/patient and 0.90 pancreas rejection/patient whereas the PE group experienced 0.53 kidney rejection/patient and 0.47 pancreas rejection/patient. The two groups were compared using incidence density statistics due to great variation in follow-up time. The SB group had a significant higher density of both kidney and pancreas rejections (p < or = 0.037 for kidney rejection and 0.058 for pancreas rejection). In addition, while 6 of 30 (20%) pancreas grafts and 4 of 30 (13%) kidney grafts were lost to irreversible rejection in the SB group, only 1 of 17 (6%) pancreas graft and 1 of 17 (6%) kidney graft were lost in the PE group. These data demonstrate, that the PE placement of pancreas allograft affects the rates of acute rejection and graft loss, and imply that there exist some important immunological advantages when the pancreas graft is drained into the portal circulation.