[关键词]
[摘要]
目的:探讨通过增强树突状细胞(dendritic cells, DC)与T细胞的相互作用来进一步增强DC介导的抗肿瘤免疫效果。方法:体外培养的小鼠骨髓DC体外经携带人MIP 1β基因的重组腺病毒(adenovirus expressing human macrophoge inflammatory protein-1 beta, AdhMIP-1β)转染后(MIP-1β-DC),用小鼠CT26结肠腺癌细胞相关抗原冲击致敏,然后免疫正常同系小鼠,观察其体内诱导的细胞毒性T淋巴细胞(cytotoxic T lymphocyte, CTL)的保护性免疫反应;通过体内阻断试验探讨免疫细胞亚群及免疫分子在DC诱导抗肿瘤免疫应答中的作用。结果:经抗原致敏的MIP-1β DC能更有效地诱导特异CTL活性,能使免疫动物产生更有效的免疫保护作用,抵抗肿瘤细胞的攻击。通过对其抗肿瘤免疫机理的分析发现,CD4+、CD8+ T 细胞共同参与了经抗原致敏的MIP-1β-DC介导的抗肿瘤免疫反应,是主要的抗瘤效应细胞,NK细胞作用不明显。结论:通过基因修饰增强树突状细胞对T细胞的体内趋化活性,能更有效地诱导抗肿瘤免疫反应,为树突状细胞介导的肿瘤免疫基因治疗开辟了新的途径。
[Key word]
[Abstract]
Objective:To probe the potent effects of dendritic cells (DCs)-based vaccine by enhancing the mutual action between DCs and T lymphocytes. Methods: Mouse bone marrow DCs transduced with human Macrophage Inflammatory Protein-1 beta (MIP-1β) gene by adenovirus vector (MIP-1β-DC) were pulsed with murine CT26 colorectal adenocarcinoma cell antigen, and used to vaccinate syngeneic mice.Results: Immunization with CT26 cell antigen-pulsed MIP-1β-DC induced specific CTL against CT26 cells and induced protective antitumor immunity, which rendered the immunized mice resistant completely to CT26 tumor challenge. The result of the study on antitumor immunity mechanism showed that the antitumor response depended on both CD8+ T cells and CD4+ T cells ,which played important roles,while NK cells were not necessary.Conclusions:MIP-1β gene modified DCs are more potent in induction of antitumor immunity through the preferential chemotaxis of DCs on T cells. Vaccination with tumor antigen-pulsed MIP-1β-DC may be a novel approach to immunotherapy of cancer.
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[基金项目]
广西科技厅资助课题(编号:桂科回0009008)