Sun Ai-Min, Li Chuan-Gang, Zhang Yu-Qin, Lin Shui-Miao, Niu Hua-Rui, Shi Yu-Sheng
Departments of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Ultrasound Diagnosis, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Cytokine. 2015 Mar;72(1):31-5. doi: 10.1016/j.cyto.2014.12.001. Epub 2015 Jan 5.
It is suggested that regulatory immune cells play a critical role in cancer cell growth by facilitating cancer cells to escape from the immune surveillance. The generation of the immune regulatory cells in cancer has not been fully understood yet. This study aims to investigate the role of the hepatoma-derived growth factor (HDGF) in the generation of regulatory T cells (Treg).
CCL-9.1 cells (A mouse hepatoma cell line), were cultured. The expression of HDGF in CCL-9.1 cells was assessed by quantitative RT-PCR and Western blotting. The generation of Foxp3(+) T cells was assessed by cell culture and flow cytometry. The immune suppressor function of the Foxp3(+) T cells on CD8(+) T cell activities was assessed by the carboxyfluorescein succinimidyl ester (CFSE)-dilution assay and enzyme-linked immunosorbent assay.
The results showed that exposure to PolyIC markedly increased the expression of HDGF in CCL-9.1 cells. Coculture of CCL-9.1 cells and CD4(+) CD25(-) T cells in the presence of PolyIC generated the Forkhead box protein (Foxp)3(+) T cells. The exposure to HDGF increased the expression of Foxp3 and decreased the expression of GATA3 in CD4(+) T cells. After activation, the Foxp3(+) T cells suppressed the CD8(+) T cell proliferation and the release of the cytotoxic cytokines.
Liver cancer cell-derived HDGF can induce Foxp3(+) T cells; the latter has the immune suppressor functions on CD8(+) T cell activities.
有研究表明，调节性免疫细胞通过促进癌细胞逃避免疫监视，在癌细胞生长中发挥关键作用。癌症中免疫调节细胞的产生尚未完全明确。本研究旨在探讨肝癌衍生生长因子（HDGF）在调节性T细胞（Treg）产生中的作用。
培养CCL-9.1细胞（一种小鼠肝癌细胞系）。通过定量逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法评估CCL-9.1细胞中HDGF的表达。通过细胞培养和流式细胞术评估Foxp3(+) T细胞的产生。通过羧基荧光素琥珀酰亚胺酯（CFSE）稀释试验和酶联免疫吸附试验评估Foxp3(+) T细胞对CD8(+) T细胞活性的免疫抑制功能。
结果显示，PolyIC刺激显著增加了CCL-9.1细胞中HDGF的表达。在PolyIC存在的情况下，将CCL-9.1细胞与CD4(+) CD25(-) T细胞共培养可产生叉头框蛋白（Foxp）3(+) T细胞。暴露于HDGF可增加CD4(+) T细胞中Foxp3的表达并降低GATA3的表达。激活后，Foxp3(+) T细胞抑制CD8(+) T细胞增殖和细胞毒性细胞因子的释放。
肝癌细胞衍生的HDGF可诱导Foxp3(+) T细胞产生；后者对CD8(+) T细胞活性具有免疫抑制功能。
