移植排斥反应是目前器官移植领域面临的重要问题，抑制受体T细胞功能是阻断器官移植后移植排斥反应的有效方法。白细胞介素-35（IL-35）可增强调节性T细胞（Treg）增殖与功能，具有抗移植排斥反应的潜力。研究证实提高器官移植受体IL-35水平能抑制移植后的排斥反应和减轻抗异基因骨髓移植的急性移植物抗宿主病。但是，目前还没有移植物局部高表达IL-35干预移植后排斥反应的相关研究。本项目利用间充质干细胞（MSC）易于被外源基因修饰以及尾静脉注射后倾向于滞留在移植肺部的特点，拟采用逆转录病毒载体修饰MSC实现IL-35的稳定表达，尾静脉注射到接受异基因肺移植的受体小鼠体内，结合生物发光成像技术探究移植肺局部IL-35过表达对肺移植急性排斥反应的作用及相关机制，为临床免疫抑制治疗提供新的有效方法。

Allograft rejection has been one important problem in the field of organ transplantation. The suppression of T cell functions of recipients gives an effective prevention of immunological rejection post transplantation. Investigations have demonstrated that interleukin-35（IL-35）shows anti-rejection potential because of its amplification and enhancement effects on Tregs cells. And some studies suggested that up-regulation of IL-35 level through IL-35 gene injection inhibited allograft rejection and mitigated acute graft-versus-host disease. However, there were no reports cocerning more benefits of high-level of IL-35 in graft post transplantation. Our previous studies indicated that mesenchymal stem cell (MSC) was easy to be genetically modified and tended to graft retention post lung transplantation. Here, to take full advantage of this property, we will achieve IL-35 local overexpression in lung grafts by retrovirus infection of MSC and intravenous injection to recipient mice received allogeneic lung transplantations. The anti-transplant rejection effect on lung transplant acute rejection will be evaluated combined bioluminescence imaging. The exploration of relevant mechanisms can provide new immunosuppressive strategy for clinical therapy.