Wang Min, Shi Jun, Wan Yun, Li Jing, Yuan Yinghua
Department of Hematology, Shanghai Jiaotong University-Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China.
In Vitro Cell Dev Biol Anim. 2009 Jul-Aug;45(7):398-404. doi: 10.1007/s11626-009-9187-4. Epub 2009 Mar 14.
Besides their role as potent antigen-presenting cells, myeloid dendritic cells (MDCs), but not plasmacytoid dendritic cells (PDCs), have been reported to have cytotoxic or cytostatic activity on some tumor cells. In this article, we analyzed the tumoristatic potential of a distinct peripheral blood monocyte-derived MDC subset which co-expressed PDC-specific marker CD123. CD123(+) MDCs represented a subset of small-sized DCs and accounted for 45-60% of peripheral blood monocytes cultured with granulocyte-macrophage colony-stimulating factor and interleukine-4 (IL-4) for 7 d. They exhibited more significant antiproliferative activity toward hematological tumor cell lines of Jurkat, HL60, and myelodysplastic syndromes over-leukemia than CD123(-) MDCs even at a low effecter/target ratio. Pretreatment of MDC and their supernatant with TRAIL-R2:Fc significantly reduced the tumoristatic effect of CD123(+) MDCs but not of CD123(-) MDCs and their supernatant. CD123(+) MDCs expressed higher level of cytoplasmic TNF-alpha-related apoptosis-inducing ligand (TRAIL) than CD123(-) MDCs, whereas both expressed very little surface and soluble TRAIL. These results reveal that CD123(+) cells represented a predominant subset of MDCs generated from peripheral blood monocytes in vitro, characterized by their potential tumoristic activity partially via cytoplasmic TRAIL.
除了作为强大的抗原呈递细胞发挥作用外，髓样树突状细胞（MDCs），而非浆细胞样树突状细胞（PDCs），已被报道对某些肿瘤细胞具有细胞毒性或细胞生长抑制活性。在本文中，我们分析了一种独特的外周血单核细胞来源的MDC亚群的肿瘤生长抑制潜力，该亚群共表达PDC特异性标志物CD123。CD123(+) MDCs代表小型DCs的一个亚群，占用粒细胞-巨噬细胞集落刺激因子和白细胞介素-4（IL-4）培养7天的外周血单核细胞的45 - 60%。即使在低效应细胞/靶细胞比例下，它们对Jurkat、HL60血液肿瘤细胞系以及骨髓增生异常综合征相关白血病的抗增殖活性也比CD123(-) MDCs更显著。用TRAIL-R2:Fc预处理MDC及其上清液可显著降低CD123(+) MDCs的肿瘤生长抑制作用，但对CD123(-) MDCs及其上清液则无此作用。CD123(+) MDCs比CD123(-) MDCs表达更高水平的细胞质肿瘤坏死因子-α相关凋亡诱导配体（TRAIL），而两者表面和可溶性TRAIL的表达都很少。这些结果表明，CD123(+)细胞代表体外由外周血单核细胞产生的MDCs的主要亚群，其特征在于部分通过细胞质TRAIL具有潜在的肿瘤生长抑制活性。
