Fiorina Paolo, Jurewicz Mollie, Tanaka Katsunori, Behazin Negin, Augello Andrea, Vergani Andrea, von Andrian Ulrich H, Smith Neal R, Sayegh Mohamed H, Abdi Reza
Transplantation Research Center (TRC), Children's Hospital and Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave., Boston, MA 02115, USA.
Diabetes. 2007 Apr;56(4):912-20. doi: 10.2337/db06-1445. Epub 2007 Feb 7.
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.
树突状细胞（DCs）是最有效的抗原呈递细胞，但关于胰岛同种异体移植排斥过程中供体和受体DCs（分别为dDCs和rDCs）的差异特征，目前可用的数据很少。DTR-GFP-DC小鼠为监测同种异体移植排斥过程中的DC迁移和特征提供了一种新工具。我们发现，早在胰岛同种异体移植后3小时，dDCs就迅速迁移到受体淋巴组织。与rDCs相比，dDCs表达不同模式的趋化因子受体，具有不同的增殖能力，并且表现出更高的成熟水平；这些发现可能归因于dDCs在胰岛细胞制备和植入过程中所遭受的损伤影响。有趣的是，在胰岛同种异体移植排斥很久之后，我们在受体的脾脏中检测到了dDCs。鉴于dDCs高表达CCR7，在移植前用CCR7的配体（CCL21）培养胰岛。这种新方法使我们能够增强dDCs从胰岛制剂中的流出，从而延长了免疫活性受体中胰岛同种异体移植的存活时间。本研究将dDCs和rDCs作为两种不同类型的DCs引入，并提供了具有临床意义的新数据，即使用基于趋化因子的DC清除策略来延长胰岛同种异体移植的存活时间。
