目的 探討體外擴增樹突狀細胞(DC)的方法,體外研究DC介導的細胞毒性T淋巴細胞(CTL)對小鼠胰腺癌的特異性殺傷作用。方法 聯合應用重組鼠源性粒細胞-巨噬細胞集落刺激因子(GM-CSF)和IL-4體外誘導骨髓源性DC,與腫瘤細胞溶解物共培養(yǎng)制備DC疫苗; 觀察DC在負載抗原后體外誘導的主動特異性CTL對胰腺癌細胞的殺傷作用。結果 用GM-CSF和 IL-4成功地在體外擴增了骨髓源性DC。 TNF-α可誘導骨髓源性DC成熟, 使其表達的CD54、主要組織相溶性復合物-Ⅱ、CD86等表面分子明顯升高,并增強自分泌IL-12和抗原的遞呈能力,與對照組比較,差異有統(tǒng)計學意義(P<0.05)。未負載腫瘤細胞抗原的DC所沖擊的T淋巴細胞不能有效地識別特定的靶細胞并產生殺傷作用,DC通過捕獲并遞呈壞死腫瘤細胞抗原才能誘發(fā)顯著的主動特異性CTL,體外對胰腺癌細胞的殺傷效果非常顯著(P<0.01)。結論 TNF-α可誘導DC的成熟,使DC的抗原遞呈和自分泌IL-12的能力顯著提高,DC遞呈抗原后能誘發(fā)顯著的主動特異性CTL。
引用本文: 譚廣,任金帥,王忠裕,殷朔. TNF-α增強樹突狀細胞誘導的抗胰腺癌免疫應答的實驗研究. 中國普外基礎與臨床雜志, 2006, 13(6): 689-692. doi: 復制
1. | Cao X, Zhang W, Wang J, et al. Therapy of established tumour with a hybrid cellular vaccine generated by using granulocyte-macrophage colony-stimulating factor genetically modified dendritic cells [J]. Immunology, 1999; 97(4)∶616. |
2. | Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor [J]. J Exp Med, 1992; 176(6)∶1693. |
3. | 秦仁義, 愛 德, 鄒聲泉, 等. 一種新型大鼠胰腺癌模型的制備 [J]. 中華實驗外科雜志, 2000; 17(5)∶462. |
4. | Cella M, Scheidegger D, Palmer-Lehmann K, et al. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation [J]. J Exp Med, 1996; 184(2)∶747. |
5. | 劉劍勇, 張力圖, 趙蔭農, 等. 樹突細胞激活的腫瘤浸潤性淋巴細胞抗肝癌免疫活性的研究 [J]. 實用癌癥雜志, 2002; 17(4)∶344. |
6. | Wang YQ, Ugai S, Shimozato O, et al. Induction of systemic immunity by expression of interleukin-23 in murine colon carcinoma cells [J]. Int J Cancer, 2003; 105(6)∶820. |
- 1. Cao X, Zhang W, Wang J, et al. Therapy of established tumour with a hybrid cellular vaccine generated by using granulocyte-macrophage colony-stimulating factor genetically modified dendritic cells [J]. Immunology, 1999; 97(4)∶616.
- 2. Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor [J]. J Exp Med, 1992; 176(6)∶1693.
- 3. 秦仁義, 愛 德, 鄒聲泉, 等. 一種新型大鼠胰腺癌模型的制備 [J]. 中華實驗外科雜志, 2000; 17(5)∶462.
- 4. Cella M, Scheidegger D, Palmer-Lehmann K, et al. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation [J]. J Exp Med, 1996; 184(2)∶747.
- 5. 劉劍勇, 張力圖, 趙蔭農, 等. 樹突細胞激活的腫瘤浸潤性淋巴細胞抗肝癌免疫活性的研究 [J]. 實用癌癥雜志, 2002; 17(4)∶344.
- 6. Wang YQ, Ugai S, Shimozato O, et al. Induction of systemic immunity by expression of interleukin-23 in murine colon carcinoma cells [J]. Int J Cancer, 2003; 105(6)∶820.