%0 Journal Article
%T Dendritic Cell-Based Approaches for Therapeutic Immune Regulation in Solid-Organ Transplantation
%A Giuseppe Vassalli
%J Journal of Transplantation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/761429
%X To avoid immune rejection, allograft recipients require drug-based immunosuppression, which has significant toxicity. An emerging approach is adoptive transfer of immunoregulatory cells. While mature dendritic cells (DCs) present donor antigen to the immune system, triggering rejection, regulatory DCs interact with regulatory T cells to promote immune tolerance. Intravenous injection of immature DCs of either donor or host origin at the time of transplantation have prolonged allograft survival in solid-organ transplant models. DCs can be treated with pharmacological agents before injection, which may attenuate their maturation in vivo. Recent data suggest that injected immunosuppressive DCs may inhibit allograft rejection, not by themselves, but through conventional DCs of the host. Genetically engineered DCs have also been tested. Two clinical trials in type-1 diabetes and rheumatoid arthritis have been carried out, and other trials, including one trial in kidney transplantation, are in progress or are imminent. 1. Introduction Allogeneic cell and solid-organ grafts trigger immune responses that cause destructive graft rejection in the absence of sustained drug-based immunosuppression [1]. Unfortunately, the latter is associated with major side effects including severe infections and cancer, especially after many years of treatment. Moreover, immunosuppressive drugs have failed to prevent chronic graft rejection, which is primarily manifested by allograft vasculopathy. The hope in the immunotherapy field is to develop a therapy that targets and neutralizes the alloimmune response selectively, while leaving protective immunity intact. Patients with a functioning allograft in the absence of maintenance immunosuppression have been described occasionally [2]. In some of them, immunosuppressive drugs were discontinued because of infection or cancer [3]. Others decided to stop taking the drugs [4]. Some liver transplant recipients were enrolled in studies of weaning immunosuppression [5]. Moreover, some kidney transplant recipients participated in studies of tolerance induction [6¨C9] which, in part, included hematopoietic cell transplantation [8, 9]. These reports demonstrate the sporadic occurrence of operational tolerance, as defined by lack of destructive graft rejection in the absence of maintenance immunosuppression [10]. Sixty years ago, Billingham et al. described ˇ°actively acquired toleranceˇ± of foreign cells. They claimed that, ˇ°if the first presentation of foreign cells takes place in fetal life, resistance to a graft [from the same donor or from
%U http://www.hindawi.com/journals/jtrans/2013/761429/