Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, P.R. China.
Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, Jiangsu 210003, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7345-7354. doi: 10.3892/mmr.2017.7581. Epub 2017 Sep 21.
Dendritic cells (DCs) as professional antigen presenting cells, are important in the initiation of the primary immune response. The present study compared the morphology, phenotypes and function between monocyte‑derived human DCs produced from a conventional culturing system containing granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) and IL‑4 (IL‑4‑DC) and DCs generated by the stimulation of GM‑CSF and interferon (IFN)‑α (IFN‑DC). When compared with IL‑4‑DC in morphology, IFN‑DC contained more organelles, including endoplasmic reticulum and myelin figures, whereas mature (m)IL‑4‑DC contained more vacuoles in the cells. The spikes of IFN‑DC were shorter and thicker. The expression of phenotypes between immature IFN‑DC and IL‑4‑DC were diverse. Following maturation with tumor necrosis factor‑α, IFN‑DC and IL‑4‑DC upregulated the expression of cluster of differentiation (CD) 11c and CD83. Conversely, immature IFN‑DC and IL‑4‑DC secreted few inflammatory cytokines including interleukin (IL)‑18, IL‑23, IL‑12p70, IL‑1β and anti‑inflammatory IL‑10. Following maturation, large amounts of the cytokines were secreted by these two DCs and mIFN‑DC secreted more cytokines compared with mIL‑4‑DC in general. Furthermore, immature IFN‑DC and IL‑4‑DC loaded with cytomegalovirus (CMV)‑pp65 protein were unable to induce the priming of T cells, as evaluated by the intracellular staining with IFN‑γ. Notably, mature DCs exhibited the ability to present CMV‑pp65 protein and activate T cells. The mIFN‑DC activated a greater proportion of autologous CD4+ T cells (0.91 vs. 0.31%, P<0.001) and CD8+ T cells (0.90 vs. 0.48%, P<0.001) to secret IFN‑γ compared with mIL‑4‑DC. The results suggested that the morphology, phenotypes and cytokine secretion of IFN‑DC and IL‑4‑DC were diverse. The mIFN‑DC were more effective in priming and cross‑priming T cells when compared with IL‑4‑DC.
树突状细胞 (DCs) 作为专业的抗原提呈细胞,在启动原发性免疫反应中起着重要作用。本研究比较了来源于含有粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 和白细胞介素 (IL)-4 (IL-4-DC) 的常规培养系统的单核细胞来源的人 DCs 与由 GM-CSF 和干扰素 (IFN)-α 刺激生成的 DCs (IFN-DC) 之间的形态、表型和功能。与形态上的 IL-4-DC 相比,IFN-DC 含有更多的细胞器,包括内质网和髓磷脂样结构,而成熟 (m)IL-4-DC 细胞内含有更多的空泡。IFN-DC 的刺较短且较厚。未成熟 IFN-DC 和 IL-4-DC 之间的表型表达存在差异。用肿瘤坏死因子-α 成熟后,IFN-DC 和 IL-4-DC 上调了分化群 (CD) 11c 和 CD83 的表达。相反,未成熟的 IFN-DC 和 IL-4-DC 分泌的炎症细胞因子较少,包括白细胞介素 (IL)-18、IL-23、IL-12p70、IL-1β 和抗炎性 IL-10。成熟后,这两种 DC 会大量分泌细胞因子,而 mIFN-DC 通常比 mIL-4-DC 分泌更多的细胞因子。此外,负载巨细胞病毒 (CMV)-pp65 蛋白的未成熟 IFN-DC 和 IL-4-DC 不能诱导 T 细胞的启动,这可通过 IFN-γ 的细胞内染色来评估。值得注意的是,成熟的 DC 能够呈递 CMV-pp65 蛋白并激活 T 细胞。与 mIL-4-DC 相比,mIFN-DC 激活了更大比例的自体 CD4+T 细胞 (0.91%比 0.31%,P<0.001) 和 CD8+T 细胞 (0.90%比 0.48%,P<0.001) 分泌 IFN-γ。结果表明,IFN-DC 和 IL-4-DC 的形态、表型和细胞因子分泌存在差异。与 IL-4-DC 相比,mIFN-DC 更有效地启动和交叉启动 T 细胞。