Tanoue Shiroh, Chang Li-Yuan, Li Yonghai, Kaplan David E
Medicine and Research Services, Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 914 BRB, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Medicine and Research Services, Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 914 BRB, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Cell Immunol. 2015 May;295(1):36-45. doi: 10.1016/j.cellimm.2015.02.008. Epub 2015 Feb 25.
Few studies have investigated the impact of liver cirrhosis on dendritic cell function. The purpose of this study was to compare the activation and antigen-presentation capacity of monocyte-derived dendritic cells (MoDC) from cirrhotic patients (CIR) relative to healthy donors (HD). MoDC from CIR and HD were matured, phenotyped, irradiated and pulsed with 15mer peptides for two hepatocellular carcinoma-related antigens, alphafetoprotein and glypican-3, then co-cultured with autologous T-cells. Expanded T-cells were evaluated by interferon-gamma ELISPOT and intracellular staining. 15 CIR and 7 HD were studied. While CD14+ monocytes from CIR displayed enhanced M2 polarization, under MoDC-polarizing conditions, we identified no significant difference between HD and CIR in maturation-induced upregulation of co-stimulation markers. Furthermore, no significant differences were observed between CIR and HD in subsequent expansion of tumor antigen-specific IFNγ+ T-cells.
MoDCs isolated from cirrhotic individuals retain similar capacity for in vitro activation, maturation and antigen-presentation as those from healthy donors.
很少有研究调查肝硬化对树突状细胞功能的影响。本研究的目的是比较肝硬化患者(CIR)与健康供体(HD)来源的单核细胞衍生树突状细胞(MoDC)的活化和抗原呈递能力。将来自CIR和HD的MoDC进行成熟、表型分析、照射,并与两种肝细胞癌相关抗原(甲胎蛋白和磷脂酰肌醇蛋白聚糖-3)的15聚体肽一起脉冲处理,然后与自体T细胞共培养。通过干扰素-γ酶联免疫斑点法和细胞内染色评估扩增的T细胞。研究了15例CIR患者和7例HD患者。虽然来自CIR的CD14 +单核细胞表现出增强的M2极化,但在MoDC极化条件下,我们发现HD和CIR在共刺激标志物成熟诱导上调方面没有显著差异。此外,在随后肿瘤抗原特异性IFNγ + T细胞的扩增中,CIR和HD之间未观察到显著差异。
从肝硬化个体分离的MoDC在体外活化、成熟和抗原呈递方面保留了与健康供体相似的能力。