Apoptotic cell-based therapies against transplant rejection: role of recipient's dendritic cells
Apoptotic cell-based therapies against transplant rejection: role of recipient's dendritic cells
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DOI：
10.1007/s10495-010-0469-9
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发表时间：
2010-09-01
期刊：
影响因子：
7.2
通讯作者：
Larregina, Adriana T.
中科院分区：
文献类型：
--
作者：
Morelli, Adrian E.;Larregina, Adriana T.
移植的最终目标之一是开发用于诱导供体特异性耐受的新的治疗方法，以减少与目前使用的药理学方案相关的全身免疫抑制引起的副作用。凋亡早期细胞的相互作用或吞噬作用对抗原呈递细胞（APC）如树突状细胞（DC）和巨噬细胞产生了强有力的抗炎和免疫抑制作用。这一观察结果导致了这样的想法，即基于凋亡细胞的疗法可以用于将供体Ag与调节信号组合递送至受体的APC，作为抑制抗供体应答的治疗方法。本文综述了凋亡细胞下调DC和巨噬细胞的免疫刺激和促炎功能的多种机制，以及凋亡细胞和APC在自体耐受和基于凋亡细胞的治疗中相互作用的作用，以预防/治疗小鼠实验系统和人类的同种异体移植物排斥反应和移植物抗宿主病。它还探讨了体内产生的凋亡细胞在体外血液分离、供体特异性输血和基于耐受性DC的移植治疗中的有益作用。
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.