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脐带血干细胞来源的树突状细胞可产生有效的抗原特异性免疫应答和抗肿瘤作用。

Cord blood stem-cell-derived dendritic cells generate potent antigen-specific immune responses and anti-tumour effects.

机构信息

Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Clin Sci (Lond). 2012 Sep;123(6):347-60. doi: 10.1042/CS20110272.

Abstract

The aim of the present study was to investigate whether CBSCs [(umbilical) cord blood stem cells] can be a new source of DCs (dendritic cells), which can generate more potent antigen-specific immune responses and anti-tumour effects. CBSCs and PBMCs (peripheral blood mononuclear cells) were collected, cultured and differentiated into DCs. Surface markers, secreting cytokines, antigen-presentation activity, antigen-specific cell-mediated immunity and cytotoxic killing effects induced by these two DC origins were evaluated and compared. CBSCs were expanded ~17-fold by ex vivo culture. The expression of surface markers in CBSC-derived DCs were higher than those in PBMC-derived DCs treated with LPS (lipopolysaccharide). The CBSC-derived DCs mainly secreted IL (interleukin)-6, IL-10 and TNF (tumour necrosis factor)-α, whereas PBMC-derived DCs mainly secreted IL-5 and IFN (interferon)-γ. The CBSC-derived DCs had better antigen-presentation abilities when stimulated with LPS or TNF-α, induced higher numbers of IFN-γ-secreting antigen-specific CD8+ T-cells, as assessed using an ELISpot (enzyme-linked immunosorbent spot) assay, and stimulated more potent antigen-specific CTL (cytotoxic T-cell) activities (P<0.01, one-way ANOVA). CBSC-derived DCs had quicker and greater ERK (extracellular-signal-regulated kinase) and Akt phosphorylation, and weaker p38 phosphorylation, than PBMC-derived DCs when stimulated with LPS. In conclusion, CBSC-derived DCs have the ability to induce stronger antigen-specific immunity and more potent anti-tumour effects and therefore could be a good source of DCs for use in DC-based cancer vaccines and immunotherapy.

摘要

本研究旨在探讨 CBSC(脐血干细胞)是否可以成为 DC(树突状细胞)的新来源,因为后者可以产生更有效的抗原特异性免疫反应和抗肿瘤作用。采集、培养和分化 CBSC 和 PBMC(外周血单个核细胞)为 DC。评估和比较这两种 DC 来源的表面标志物、分泌细胞因子、抗原呈递活性、抗原特异性细胞介导的免疫和细胞毒性杀伤效应。CBSC 经体外培养可扩增约 17 倍。CBSC 来源的 DC 表面标志物的表达高于 LPS(脂多糖)处理的 PBMC 来源的 DC。CBSC 来源的 DC 主要分泌 IL(白细胞介素)-6、IL-10 和 TNF(肿瘤坏死因子)-α,而 PBMC 来源的 DC 主要分泌 IL-5 和 IFN(干扰素)-γ。LPS 或 TNF-α刺激后,CBSC 来源的 DC 具有更好的抗原呈递能力,通过 ELISpot(酶联免疫斑点)测定诱导更多数量的 IFN-γ 分泌的抗原特异性 CD8+T 细胞,并且刺激更强的抗原特异性 CTL(细胞毒性 T 细胞)活性(P<0.01,单因素方差分析)。与 PBMC 来源的 DC 相比,LPS 刺激时 CBSC 来源的 DC 具有更快和更强的 ERK(细胞外信号调节激酶)和 Akt 磷酸化,以及较弱的 p38 磷酸化。总之,CBSC 来源的 DC 具有诱导更强的抗原特异性免疫和更有效的抗肿瘤作用的能力,因此可能是用于基于 DC 的癌症疫苗和免疫治疗的良好 DC 来源。

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