Donor Apoptotic Lymphocyte Transfusion-Induced Liver Allograft Tolerance by Up-Regulation of CD4+CD25+ Regulatory T Cells in Peripheral Blood

Uptake of apoptotic cells by antigen-presenting cells (APC) may be involved in tolerance maintenance with an immunoregulatory role. The aim of this study was to evaluate the consequences of preoperative transfusion of donor apoptotic lymphocytes on survival of orthotopic liver transplantations (OLT). OLT was performed between Lewis (donor) and Brown Norway (BN recipient) inbred rats using a double-cuff technique. Apoptotic splenic lymphocytes induced by ultraviolet-C (UVC) irradiation were infused intravenously at 7 days before OLT. Changes in regulatory T cells in blood were determined using flow cytometry. UVC irradiated lymphocytes were sensitive and effective, as evidenced by increased peripheral blood CD4(+)CD25(+) T cells compared with recipients that received infusion of untreated donor lymphocytes or a control. Apoptotic lymphocyte transfusion prolonged hepatic allograft survival, with significantly lower histological stages of inflammation and cellular infiltration than in untreated allografts. Our results demonstrated that donor apoptotic cells promoted allograft acceptance and up-regulated CD4(+)CD25(+) regulatory T cells (Treg) in blood.