Apoptotic cell-based therapies against transplant rejection: role of recipient's dendritic cells.
One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient's APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation.
Morelli
Adrian E
AE
T.E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, PA 15213-2582, USA. morelli@imap.pitt.edu
Larregina
Adriana T
AT
D000818:Animals; D017209:Apoptosis; D017690:Cell Transplantation; D064987:Cell- and Tissue-Based Therapy; D003713:Dendritic Cells / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007165:Immunosuppression Therapy; D051379:Mice