Effects of IL‐10‐ and FasL‐overexpressing dendritic cells on liver transplantation tolerance in a heterotopic liver transplantation rat model

Acute rejection is the major determinant for the long‐term survival of donor liver after liver transplantation (LT). The aim of this study was to examine the therapeutic potential of interleukin (IL)‐10‐FasL‐overexpressing immature dendritic cells (imDCs) to induce local immunosuppression in liver grafts. imDCs derived from donors were transduced by lentiviral vectors expressing human IL‐10 and/or Fas ligand (FasL) gene(s), and the expression of surface molecules and the ability to induce T‐cell proliferation were measured. imDCs were intraperitoneally injected into recipient rats as a model of LT to examine the rejection grade [Banff rejection activity index (RAI)], liver functions [Alanine aminotransferase, Aspartate aminotransferase (AST) and total bilirubin (TBIL)] and post‐transplant survival. IL‐10 and FasL co‐transduction of imDCs induced a greater reduction in CD80, CD86 and major histocompatibility complex class II (MHC II) expression, as well as T‐cell proliferation, but increased levels of IL‐10 and FasL in culture supernatants compared with mono‐transduced or untransduced imDCs (P