Fontana A, Bodmer S, Frei K, Malipiero U, Siepl C
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Ciba Found Symp. 1991;157:232-8; discussion 238-41. doi: 10.1002/9780470514061.ch15.
Glioblastomas are among the most malignant tumours for which no curative treatment exists. A dysfunction of cellular immunity with decreased skin reactivity and lymphocyte blastogenesis has been described in patients with glioblastomas. In culture human glioblastoma cells release a factor termed glioblastoma-derived T cell suppressor factor (G-TsF) which inhibits the antigen-dependent growth of both helper and cytotoxic T cells. Purification and cloning indicated that G-TsF is a novel member of the TGF-beta family with a well-conserved mature sequence but less homology in the precursor segments. The factor was renamed TGF-beta 2. The two glioblastoma cell lines investigated expressed mRNAs for both G-TsF/TGF-beta 2 and TGF-beta 1 but only G-TsF/TGF-beta 2 protein was secreted. Neuroblastoma cells express only the mRNA for TGF-beta 1 but not the protein, nor the mRNA for G-TsF/TGF-beta 2. Recombinant G-TsF/TGF-beta 2 inhibits the generation of virus-specific cytotoxic T cells when injected into mice infected with lymphocytic choriomeningitis virus. Thus G-TsF/TGF-beta 2 might contribute to the impairment of tumour immune surveillance. Some T cell clones may escape the immunosuppressive effects of TGF-beta: ovalbumin-specific T helper cell lines that showed different degrees of susceptibility to TGF-beta contained clones which had lost receptor(s) for TGF-beta.
胶质母细胞瘤是最恶性的肿瘤之一，目前尚无治愈性治疗方法。已有研究报道，胶质母细胞瘤患者存在细胞免疫功能障碍，表现为皮肤反应性降低和淋巴细胞母细胞生成减少。在培养过程中，人胶质母细胞瘤细胞释放一种称为胶质母细胞瘤衍生的T细胞抑制因子（G-TsF）的因子，该因子可抑制辅助性T细胞和细胞毒性T细胞的抗原依赖性生长。纯化和克隆表明，G-TsF是转化生长因子-β（TGF-β）家族的一个新成员，其成熟序列高度保守，但前体片段的同源性较低。该因子随后被重新命名为TGF-β2。所研究的两种胶质母细胞瘤细胞系均表达G-TsF/TGF-β2和TGF-β1的mRNA，但仅分泌G-TsF/TGF-β2蛋白。神经母细胞瘤细胞仅表达TGF-β1的mRNA，不表达该蛋白，也不表达G-TsF/TGF-β2的mRNA。重组G-TsF/TGF-β2注射到感染淋巴细胞性脉络丛脑膜炎病毒的小鼠体内时，可抑制病毒特异性细胞毒性T细胞的产生。因此，G-TsF/TGF-β2可能导致肿瘤免疫监视功能受损。一些T细胞克隆可能逃避TGF-β的免疫抑制作用：对TGF-β表现出不同程度敏感性的卵清蛋白特异性T辅助细胞系中，含有已失去TGF-β受体的克隆。
