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目的研究含非甲基化 CpG 基序的寡核苷酸(CpG-ODN)对慢性乙型肝炎患者(CHB)外周血树突状细胞(DC)表型和功能的影响。方法以 CD14磁性分选微珠分离 CHB 患者外周血高纯度单核细胞;以重组人粒细胞巨噬细胞集落刺激因子(hGM-CSF)、重组人白细胞介素-4(hIL-4)诱导扩增 DC;以 CpG-ODN 刺激 DC 成熟,并与肿瘤坏死因子(TNF)-α比较,评价其对 DC 表达表面分子人类白细胞组织相容性抗原(HLA)-DR、CD86、CD1a,分泌 IL-12p70以及刺激同种 T 细胞增殖能力的影响。结果与 non-ODN 和磷酸盐缓冲液(PBS)组比较,CpG-ODN 能明显提高 CHB 患者外周血 DC 表面分子 HLA-DR、CD86的表达,使 IL-12分泌增加,刺激同种异体 T 细胞增殖的能力亦显著增强(P=0.017和0.023),但不能明显提高 CD1a 的表达;CpG-ODN 的上述刺激作用接近或略逊于hTNF-α,但差异无统计学意义(P>0.05)。结论 CpG-ODN 与 hTNF-α一样能够促进 CHB 患者外周血 DC 成熟进而增强其抗原提呈功能。
Objective To investigate the effects of CpG-ODN containing unmethylated CpG motifs on the phenotype and function of peripheral blood dendritic cells (DCs) in patients with chronic hepatitis B (CHB). Methods CD14 magnetic beads were used to isolate high purity monocytes from peripheral blood of patients with CHB. Recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF) and recombinant human interleukin-4 (hIL-4) DCs were stimulated with CpG-ODN and compared with tumor necrosis factor-α (TNF-α) to evaluate their effect on the expression of HLA-DR, CD86, CD1a and IL- 12p70 and stimulate the proliferation of allogeneic T cells. Results Compared with non-ODN and phosphate buffered saline (PBS) groups, CpG-ODN significantly increased the expression of HLA-DR and CD86 on peripheral blood mononuclear cells in CHB patients, increased the secretion of IL-12 and stimulated allogeneic T cells (P = 0.017 and 0.023), but not significantly increased the expression of CD1a. The above stimulation of CpG-ODN was similar to or less than that of hTNF-α, but the difference was not statistically significant (P> 0.05). Conclusions CpG-ODN, like hTNF-α, can promote DC maturation in peripheral blood of CHB patients and enhance its antigen presenting function.