QIMR Berghofer Medical Research Institute, Brisbane City, QLD 4029, Australia.
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
Immunity. 2016 Aug 16;45(2):333-45. doi: 10.1016/j.immuni.2016.07.017.
Many pathogens, including Plasmodium spp., exploit the interaction of programmed death-1 (PD-1) with PD-1-ligand-1 (PD-L1) to "deactivate" T cell functions, but the role of PD-L2 remains unclear. We studied malarial infections to understand the contribution of PD-L2 to immunity. Here we have shown that higher PD-L2 expression on blood dendritic cells, from Plasmodium falciparum-infected individuals, correlated with lower parasitemia. Mechanistic studies in mice showed that PD-L2 was indispensable for establishing effective CD4(+) T cell immunity against malaria, because it not only inhibited PD-L1 to PD-1 activity but also increased CD3 and inducible co-stimulator (ICOS) expression on T cells. Importantly, administration of soluble multimeric PD-L2 to mice with lethal malaria was sufficient to dramatically improve immunity and survival. These studies show immuno-regulation by PD-L2, which has the potential to be translated into an effective treatment for malaria and other diseases where T cell immunity is ineffective or short-lived due to PD-1-mediated signaling.
许多病原体，包括疟原虫属，利用程序性死亡受体 1（PD-1）与 PD-1 配体 1（PD-L1）的相互作用来“失活”T 细胞功能，但 PD-L2 的作用尚不清楚。我们研究了疟疾感染，以了解 PD-L2 对免疫的贡献。在这里，我们已经表明，来自疟原虫感染个体的血液树突状细胞上更高的 PD-L2 表达与更低的寄生虫血症相关。在小鼠中的机制研究表明，PD-L2 对于建立针对疟疾的有效 CD4(+)T 细胞免疫是必不可少的，因为它不仅抑制 PD-L1 对 PD-1 的活性，而且还增加了 T 细胞上的 CD3 和诱导共刺激（ICOS）表达。重要的是，向患有致死性疟疾的小鼠施用可溶性多聚体 PD-L2 足以显著改善免疫和存活。这些研究表明 PD-L2 的免疫调节作用，它有可能转化为一种有效的疟疾治疗方法，以及其他由于 PD-1 介导的信号导致 T 细胞免疫无效或短暂的疾病的治疗方法。
