[Glial tumor cell proliferation and immune response in the brain]

The mechanism of glial tumor cell proliferation and the immune response to glioma cells in the brain were examined both in vitro and in vivo experimental systems, using mouse malignant glioma cell line, 203-glioma. A fura-2 fluorescence image showed marked rise in the intracellular calcium ion concentration in mechanically stimulated single cells. The increased calcium spread to adjacent cells, probably due to some stimulating factor released from cells. Dye microinjection revealed no gap junction between cells. Antagonists of voltage-dependent calcium channels did not act on the calcium response. These suggest that calcium signaling in the glioma cells may be mediated via a membrane receptor but not through a gap junction. Depletion of extracellular calcium ion and addition of intracellular calcium blocker demonstrated that calcium signaling in stimulated cells may be related to both an influx of extracellular calcium and a redistribution of intracellular calcium from internal stores, whereas calcium transmission to adjacent cells may involve calcium influx alone. The splenic cytotoxic T lymphocyte (CTL) activity in intracerebral tumor-bearing hosts increased with a peak 2 weeks after tumor cell inoculation, but rapidly decreased concurrently with increased intracranial pressure. The major histocompatibility complex, MHC, class I antigen expression on tumor cells grafted intracerebrally was found to enhance markedly, resulting in an increase in susceptibility to CTL. It was suggested that there may be a positive correlation between the cell surface MHC class I antigen expression and sensitivity to CTL in glioma cells.