Jachimczak P, Bogdahn U, Schneider J, Behl C, Meixensberger J, Apfel R, Dörries R, Schlingensiepen K H, Brysch W
Department of Neurology, University of Würzburg, Germany.
J Neurosurg. 1993 Jun;78(6):944-51. doi: 10.3171/jns.1993.78.6.0944.
This in vitro study was aimed at restitution of transforming growth factor (TGF)-beta 2-mediated suppression of T-lymphocyte activation within malignant gliomas. In early-passage tumor cell cultures of two glioblastomas (HTZ-153 and HTZ-209) and one malignant astrocytoma classified as World Health Organization Grade III (HTZ-243), autologous peripheral blood mononuclear cells were activated by interleukin-1 alpha and interleukin-2 in vitro (lymphokine-activated killer cells) and tested for cytotoxic and proliferative activity. In expression studies (Western blot and Northern hybridization) of all three tumors, TGF-beta could be detected at the protein and messenger ribonucleic acid (mRNA) levels. A polyclonal anti-TGF-beta neutralizing antibody did not enhance lymphocyte proliferation upon stimulation with tumor targets (3H-thymidine incorporation) and slightly stimulated lymphocyte cytotoxicity against autologous target cells. Preincubation of target cells for 12 hours with TGF-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides (S-ODN's) did, however, enhance lymphocyte proliferation up to 2.5-fold and autologous tumor cytotoxicity up to 60%, compared to controls not treated with S-ODN's. Incubation of tumor cells with TGF-beta 2-specific S-ODN's resulted in decreased TGF-beta-specific immunoreactivity in cultured glioma cells, in reduced TGF-beta 2 protein concentration (Western blot), and in a change in the expression pattern of TGF-beta 2 mRNA's. These observations may have implications for in vivo and in vitro activation of a cellular immune response against autologous malignant glioma cells.
这项体外研究旨在恢复转化生长因子（TGF）-β2介导的对恶性胶质瘤内T淋巴细胞激活的抑制作用。在两种胶质母细胞瘤（HTZ-153和HTZ-209）以及一种被分类为世界卫生组织III级的恶性星形细胞瘤（HTZ-243）的早期传代肿瘤细胞培养物中，自体外周血单核细胞在体外被白细胞介素-1α和白细胞介素-2激活（淋巴因子激活的杀伤细胞），并检测其细胞毒性和增殖活性。在对所有三种肿瘤的表达研究（蛋白质印迹法和Northern杂交）中，可在蛋白质和信使核糖核酸（mRNA）水平检测到TGF-β。一种多克隆抗TGF-β中和抗体在肿瘤靶标刺激下（3H-胸腺嘧啶核苷掺入）并未增强淋巴细胞增殖，且对自体靶细胞的淋巴细胞细胞毒性有轻微刺激作用。然而，与未用硫代磷酸酯-反义寡脱氧核苷酸（S-ODN）处理的对照相比，用TGF-β2特异性硫代磷酸酯-反义寡脱氧核苷酸（S-ODN）对靶细胞进行12小时预孵育可使淋巴细胞增殖增强达2.5倍，自体肿瘤细胞毒性增强达60%。用TGF-β2特异性S-ODN孵育肿瘤细胞导致培养的胶质瘤细胞中TGF-β特异性免疫反应性降低、TGF-β2蛋白浓度降低（蛋白质印迹法）以及TGF-β2 mRNA表达模式改变。这些观察结果可能对针对自体恶性胶质瘤细胞的细胞免疫反应的体内和体外激活具有重要意义。
