2019年03月，孙爱宁教授、吴德沛教授研究团队在Archivum Immunologiae etTherapiae Experimentalis杂志以研究论文形式发表了关于最新研究成果“PD-L1 Ameliorates Murine AcuteGraft-Versus-Host Disease by Suppressing Effector But Not Regulatory T CellsFunction”。该研究成果证明在小鼠aGVHD模型中，PD-L1通过抑制效应T细胞的功能来改善小鼠aGVHD，而非通过Treg细胞途径。
异基因造血干细胞移植(allo-HSCT)是治疗血液系统恶性疾病最有效的治疗方法之一。然而，移植后的移植物抗宿主病（graft-versus-host disease，GVHD）却严重影响患者的预后及生存率。近年来主要通过抑制供体T细胞的功能或者清楚移植物中的T细胞，以此预防及减轻GVHD，但是这些手段却会影响移植后的免疫重建过程，增加病人的感染风险，并且减弱了移植物抗白血病反应。因此，寻找抑制aGVHD的异基因造血干细胞移植方案是提高患者生存率、改善其预后急需解决的关键问题。
PD-1是一种负性凋控因子，主要表达于活化的T细胞表面。PD-1与其配体（PD-L1，PD-L2）相互作用在维持自身免疫耐受和自身免疫疾病中发挥重要的调节作用。PD-L1主要表达于CD4和CD8 T细胞、B细胞、单个核细胞、自然杀伤细胞及树突状细胞中，在细胞活化的时候会发生上调。PD-L2的表达较少，主要表达于树突状细胞和巨噬细胞上。
本课题研究首次证明了系统性过表达PD-L1通过抑制效应T细胞增殖、活化，促进其凋亡，以此改善小鼠aGVHD，而非通过Treg细胞依赖途径发挥其作用。本课题的研究结果为临床使用PD-L1蛋白治疗及预防aGVHD提供了理论基础。
原文摘要：
Thereis increasing evidence that interaction between programmed death 1 (PD-1) andits ligands PD-1 (PD-L1) plays a critical role in the pathology of acute graft-versus-hostdisease (aGVHD). However, the role of PD-L1 in the development of aGVHD hasbeen controversial in recent mouse studies. In this study, we carried outstudies in a murine aGVHD model to clarify the role of PD-L1 in aGVHDpathogenesis. We found that systemic overexpression of PD-L1 by hydrodynamicgene transfer (HGT) method in vivo ameliorates aGVHD-induced lethality in mice.Systemic overexpression of PD-L1 inhibits the donor T cells activation,effector memory status, as well as Th1 and Th17 cells responses in vivo. Inaddition, PD-L1 Ig treatment significantly suppressed T cells’ proliferation,promoted T cells’ apoptosis, and reduced pro-inflammatory cytokines
expression by effector T cells in vitro in the stimulation ofanti-CD3/CD28 and allogeneic dendritic cells. However, we found that PD-L1overexpression did not affect Treg cells’ differentiation in vivo and in vitro,depletion of Treg cells in PD-L1 HGT recipients did not aggravate aGVHDmortality. Therefore, our results demonstrated that systemic treatment withPD-L1 protein ameliorates aGVHD by suppressing effector but not regulatory Tcell function. Our findings suggest that systemic treatment with PD-L1 may be apotential strategy to prevent or ameliorate aGVHD.
