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Apoptotic cell-based therapies against transplant rejection: role of recipient s dendritic cells Morelli AE; Larregina ATApoptosis 2010[Sep]; 15 (9): 1083-97One 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.|*Apoptosis[MESH]|*Cell Transplantation[MESH]|*Graft Rejection/immunology[MESH]|*Immunosuppression Therapy[MESH]|Animals[MESH]|Cell- and Tissue-Based Therapy[MESH]|Dendritic Cells/*immunology[MESH]|Graft vs Host Disease/*immunology/physiopathology[MESH]|Humans[MESH]|Mice[MESH] |
