Characterization of donor dendritic cells and enhancement of dendritic cell efflux with cc-chemokine ligand 21 - A novel strategy to prolong islet allograft survival
Characterization of donor dendritic cells and enhancement of dendritic cell efflux with cc-chemokine ligand 21 - A novel strategy to prolong islet allograft survival
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DOI：
10.2337/db06-1445
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发表时间：
2007-04-01
期刊：
影响因子：
7.7
通讯作者：
Abdi, Reza
中科院分区：
文献类型：
--
作者：
Fiorina, Paolo;Jurewicz, Mollie;Abdi, Reza
树突状细胞(DC)是最有效的抗原提呈细胞，但供受体DC(分别为DDCS和RDC)在同种异体胰岛移植排斥反应过程中的差异特征研究较少。DTR-GFP-DC小鼠提供了一种新的工具来监测DC在同种异体移植排斥反应中的运输和特征。我们发现，早在同种异体胰岛移植后3小时，DDCS就迅速向受体淋巴组织迁移。与RDC相比，DDCs表达不同的趋化因子受体模式，表现出不同的增殖能力，并表现出更高的成熟度；这些结果可能归因于DDCs在胰岛细胞准备和植入过程中遭受的损伤。有趣的是，我们在同种异体胰岛移植排斥反应后很久的受者的脾中发现了DDCS。由于DDCs表达高水平的CCR7，移植前胰岛与CCR7(CCL21)的配体一起培养。这一新方法使我们能够增加胰岛制剂中DDCS的外流，从而延长了免疫功能受者的同种胰岛移植物存活时间。这项研究介绍了DDCS和RDC作为两种不同类型的DC，并为使用基于趋化因子的DC耗竭策略延长同种异体胰岛移植物存活提供了具有临床意义的新数据。
Dendritic cells (DCs) are the most potent antigen-presenting cells, yet little data are available on the differential characteristics of donor and recipient DCs (dDCs and rDCs, respectively) during the process of islet allograft rejection. DTR-GFP-DC mice provide a novel tool to monitor DC trafficking and characteristics during allograft rejection. We show rapid migration of dDCs to recipient lymphoid tissues as early as 3 h post-islet allotransplantation. Compared with rDCs, dDCs express different patterns of chemokine receptors, display differential proliferative capacity, and exhibit a higher level of maturity; these findings could be attributed to the effects of injury that dDCs undergo during islet cell preparation and engraftment. Intriguingly, we detected dDCs in the spleen of recipients long after rejection of islet allografts. Given that dDCs express high levels of CCR7, islets were cultured before transplant with the ligand for CCR7 (CCL21). This novel method, which enabled us to enhance the efflux of dDCs from islet preparations, resulted in a prolongation of islet allograft survival in immunocompetent recipients. This study introduces dDCs and rDCs as two distinct types of DCs and provides novel data with clinical implications to use chemokine-based DC-depleting strategies to prolong islet allograft survival.