The mechanisms of demyelinating neurological diseases

为了探讨中枢神经系统炎性脱髓鞘的发生机制，我们首先研究了少突胶质细胞与免疫系统的相互作用。无论是淋巴因子，单核细胞，也不是髓鞘碱性蛋白（MBP）反应性T细胞的细胞毒性，在体外分离的小鼠少突胶质细胞。小胶质细胞和星形胶质细胞未能提出MBP抗原的MBP反应性T细胞系，虽然这两种细胞类型诱导表达Ia抗原的γ-干扰素。粗品淋巴因子被发现，以促进少突胶质细胞的成熟，而不是有毒的这些cells.Second，我们分析了在中枢神经系统中的细胞因子的生产和病理生理功能。小胶质细胞产生白细胞介素（IL）-1，6、TNF-α和另一种诱导星形胶质细胞增殖的未知因子。该因子可能在神经胶质增生的发展中起作用。除了这些细胞因子外，星形胶质细胞还产生M-CSF、GM-CSF、TGF-β和其他未知因子，其中一种因子促进内皮细胞形成紧密连接，另一种因子抑制小胶质细胞的功能。逆转录病毒感染和转染人T细胞白血病病毒1型反式激活因子也诱导星形胶质细胞产生IL-1和IL-6，但不诱导TNF-α的产生。这种转染也诱导I类主要组织相容性复合物抗原在这些神经胶质细胞上的表面表达。由于MHC抗原过表达可诱导少突胶质细胞损伤，因此该转染模型可能是诱导髓鞘脱失或髓鞘发育不良的有用工具。这些观察结果表明，免疫调节细胞因子在CNS中产生，并且这些细胞因子可能在神经细胞的细胞-细胞相互作用中起重要作用。病毒可能是这些细胞因子的诱导物，这些细胞因子在包括炎性脱髓鞘在内的各种神经系统疾病的发生发展中起重要作用。

In order to approach the mechanisms of inflammatory demyelination in the central nervous system, we first examined the interaction between oligodendrocytes and immune system. Neither lymphokines, monokisses nor myelin basic protein (MBP) -reactive T cells were cytotoxic to isolated mouse oligodendrocytes in vitro. Microglia and astrocytes failed to present MBP antigen to the MBP-reactive T cell lines, though both cell types were induced to express Ia antigens by gamma-interferon. Crude lymphokines were found to facilitate maturation of oligodendrocytes rather than toxic to these cells.Second, we analysed the production and pathophysiological functions of cytokines in the CNS. Microglia produced interleukin (IL) -1, 6, TNF-alpha and another unknown factor which induced astrocyte proliferation. This factor may have a role in the development of gliosis. In addition to these cytokines, astrocytes produced M-CSF, GM-CSF, TGF-beta and other unknown factors, one of which facilitated tight junction formation by endothelial cells, and the other factor suppressed the functions of microglia. TGF-beta also suppress the cytokine production by microglia.Retrovirus infection and transfection of Human T-cell Leukemia Virus Type 1 transactivator also induced IL-1 and IL-6 production, but not TNF-alpha production, by astrocytes. This transfection also induced surface expression of class I major histocompatibility complex antigens on these glial cells. Since overexpression of MHC antigens reportedly induces oligodendrocyte damage, this transfection model may be useful tool to induce de- or dysmyelination.These observations suggested that immunoregulatory cytokines were produced in the CNS, and these cytokines might play a important role on the cell-cell interaction in neural cells. Virus could be a possible inducer of these cytokines, which then play a significant role on the development of various neurological disorders including inflammatory demyelination.