Carter Jeffrey D, Ellett Justin D, Chen Meng, Smith Kellie M, Fialkow Lawrence B, McDuffie Marcia J, Tung Kenneth S, Nadler Jerry L, Yang Zandong
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Mol Ther. 2005 Aug;12(2):360-8. doi: 10.1016/j.ymthe.2005.02.030.
Protection of transplanted pancreatic islet grafts in recipients with autoimmune diabetes depends on the suppression of autoimmune recurrence and allogeneic rejection. The aim of this study was to investigate the efficiency of viral IL-10 gene delivery in the prevention of autoimmune recurrence following islet transplantation. We evaluated the effectiveness of a systemically delivered adeno-associated viral vector (AAV vIL-10) carrying viral IL-10 in protecting islet engraftment. We observed significant prolongation of graft survival after treatment with AAV vIL-10 when using islets from donors lacking autoimmunity. We found that the mechanism of vIL-10-mediated protection was associated with suppression of T cell activation and that donor immune cells that were simultaneously transferred with the islet grafts could induce autoimmune recurrence. AAV vIL-10 gene transfer suppressed previously activated T cells and protected grafted islets from autoimmune-mediated destruction. We conclude that vIL-10 can regulate autoimmune activity and that transfer of its gene may have potential for therapeutic islet transplantation.
在患有自身免疫性糖尿病的受体中，移植胰岛移植物的保护取决于自身免疫复发和同种异体排斥反应的抑制。本研究的目的是调查病毒白细胞介素-10基因递送在预防胰岛移植后自身免疫复发方面的效率。我们评估了携带病毒白细胞介素-10的系统性递送腺相关病毒载体（AAV vIL-10）在保护胰岛植入方面的有效性。当使用来自缺乏自身免疫性的供体的胰岛时，我们观察到用AAV vIL-10治疗后移植物存活时间显著延长。我们发现vIL-10介导的保护机制与T细胞活化的抑制有关，并且与胰岛移植物同时转移的供体免疫细胞可诱导自身免疫复发。AAV vIL-10基因转移抑制了先前活化的T细胞，并保护移植的胰岛免受自身免疫介导的破坏。我们得出结论，vIL-10可调节自身免疫活性，其基因转移可能对治疗性胰岛移植具有潜力。
