Programmed Death-1 and Its Ligand Are Novel Immunotolerant Molecules Expressed on Leukemic B Cells in Chronic Lymphocytic Leukemia

Programmed death-1 (PD-1) is an immunoreceptor predominantly expressed on exhausted T cells, which through an interaction with its ligand (PD-L1), controls peripheral tolerance by limiting effector functions of T lymphocytes. qRT-PCR for PD-1, PD-L1 and their splicing forms as well as flow cytometric assessment of surface expression was performed in a cohort of 58 chronic lymphocytic leukemia (CLL) patients. In functional studies, we assessed the influence of the proliferative response of leukemic B-cells induced by IL-4 and CD40L on PD-1 transcripts and expression on the protein level. The median level of PD-1, but not PD-L1, transcripts in CLL patients was higher in comparison to healthy volunteers (HVs, n = 43, p = 0.0057). We confirmed the presence of PD-1 and PD-L1 on the CLL cell surface, and found the expression of PD-1, but not PD-L1, to be higher among CLL patients in comparison to HVs (47.2% vs. 14.8%, p程序性死亡蛋白1（Programmed death-1, PD-1）是一类主要在耗竭T细胞上表达的免疫受体，通过与其配体PD-L1结合，可通过限制T淋巴细胞的效应功能调控外周免疫耐受。本研究对58例慢性淋巴细胞白血病（chronic lymphocytic leukemia, CLL）患者队列中的PD-1、PD-L1及其剪接变体开展了实时定量逆转录聚合酶链反应（qRT-PCR）检测，并通过流式细胞术分析了其表面表达情况。在功能实验中，我们评估了白细胞介素4（IL-4）与CD40配体（CD40L）诱导的白血病B细胞增殖反应对PD-1转录本及蛋白水平表达的影响。结果显示，与健康志愿者（HVs，n=43，p=0.0057）相比，CLL患者体内PD-1转录本的中位水平显著升高，而PD-L1转录本水平无此差异。本研究证实了CLL细胞表面存在PD-1与PD-L1的表达，且与健康志愿者相比，CLL患者的PD-1表达水平更高（47.2% vs. 14.8%，p = ）