Giraudon P, Bernard A, Malcus C, Dufay N, Desgranges C, Belin M F
U433 INSERM, Laboratoire Anatomie Pathologique, Faculte de Medicine Alexis Carrel, Lyon, France.
J Neuropathol Exp Neurol. 1995 Mar;54(2):165-74. doi: 10.1097/00005072-199503000-00003.
Primitive neuroectodermal tumors are thought to result from disturbed differentiation of neuroepithelial stem cells. These tumor cells retain the capacity to differentiate toward the neuron or glia phenotype under extrinsic stimuli. Previously, we have developed a model for the differentiation of a medulloblastoma cell line (Dev cells) induced by infection with the human retrovirus HTLV-I. This virus delivers signals which trigger the Dev cells to differentiate toward an astrocytic lineage. The aim of this study was to characterize the time course of viral infection, to identify the soluble factors released and to analyze their effects on Dev cells. The early phase of viral replication is followed by latent infection. Viral infection induces glial differentiation in a subpopulation of cells and results in the death of others. The inflammatory cytokines TNF alpha, IL1 alpha and IL6 were detected in medium conditioned by infected Dev cells. TNF alpha was cytotoxic and cytostatic for subpopulations of Dev cells. Furthermore, TNF alpha treatment reproduced the modulation of expression of the major histocompatibility complex antigens (MHC class I) observed in infected Dev cells. These observations support the view that HTLV-I infection, which triggers glial differentiation of medulloblastoma Dev cells, also causes the release of soluble factors capable of downregulating proliferation of dividing tumor cells and of modifying their recognition by cellular immune effectors.
原始神经外胚层肿瘤被认为是神经上皮干细胞分化紊乱所致。这些肿瘤细胞在外源刺激下仍保留向神经元或神经胶质表型分化的能力。此前，我们建立了一个模型，用于研究人逆转录病毒HTLV-I感染诱导的髓母细胞瘤细胞系（Dev细胞）的分化。这种病毒传递信号，促使Dev细胞向星形胶质细胞谱系分化。本研究的目的是描述病毒感染的时间进程，鉴定释放的可溶性因子，并分析它们对Dev细胞的影响。病毒复制的早期阶段之后是潜伏感染。病毒感染在一部分细胞中诱导神经胶质分化，并导致其他细胞死亡。在感染Dev细胞的条件培养基中检测到炎性细胞因子TNFα、IL1α和IL6。TNFα对Dev细胞亚群具有细胞毒性和细胞生长抑制作用。此外，TNFα处理重现了在感染Dev细胞中观察到的主要组织相容性复合体抗原（I类MHC）表达的调节。这些观察结果支持这样一种观点，即HTLV-I感染触发髓母细胞瘤Dev细胞的神经胶质分化，同时也导致可溶性因子的释放，这些因子能够下调分裂肿瘤细胞的增殖，并改变细胞免疫效应器对它们的识别。
