The susceptibility of mice to immune-mediated neurologic disease correlates with the degree to which their lymphocytes resist the effects of brain-derived gangliosides.
The susceptibility of mice to immune-mediated neurologic disease correlates with the degree to which their lymphocytes resist the effects of brain-derived gangliosides.
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DOI：
10.4049/jimmunol.161.6.2746
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发表时间：
1998-09
影响因子：
4.4
通讯作者：
D. Irani
中科院分区：
文献类型：
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作者：
D. Irani
SJL小鼠在感染某些嗜神经病毒或用髓磷脂Ag免疫时发生免疫介导的中枢神经系统（CNS）病症。包括BALB/c在内的其他菌株对这些疾病更具抵抗力。在辛德毕斯病毒诱导的脑炎期间，两种小鼠都很容易感染，并在大脑中引起快速的单核细胞炎症。然而，只有SJL小鼠发生免疫介导的瘫痪; BALB/c小鼠保持无症状。为了了解相同的刺激如何对宿主产生如此不同的免疫效应，本研究调查了从辛德毕斯病毒感染动物的大脑中分离的淋巴细胞。从SJL小鼠的脑细胞表现出更多的增殖，产生更多的IL-2，保持更高的活力，并表达较少的bax mRNA（促凋亡介质）比淋巴细胞从BALB/c小鼠的脑。由于中枢神经系统富含在体外调节T细胞增殖和IL-2产生的神经节苷脂，因此在来自两种菌株的外周淋巴细胞上测试纯化的脑源性神经节苷脂。与BALB/c小鼠相比，这些脂质对SJL小鼠淋巴细胞中丝裂原诱导的增殖、IL-2产生、活化诱导的细胞死亡和bax mRNA上调的影响较小。因此，与SJL小鼠的脑相比，神经节苷脂可以抑制BALB/c小鼠脑中的各种T细胞效应器功能，并在更大程度上诱导T细胞凋亡。这种局部淋巴细胞调节的相对缺陷可能会增强SJL小鼠对免疫介导的神经系统疾病的易感性。
SJL mice develop immune-mediated disorders of the central nervous system (CNS) when infected with certain neurotropic viruses or when immunized with myelin Ags. Other strains including BALB/c are more resistant to these diseases. During Sindbis virus-induced encephalitis, both mice are easily infected and elicit rapid mononuclear cell inflammation in the brain. However, only SJL mice develop immune-mediated paralysis; BALB/c mice remain asymptomatic. To understand how the same stimulus produces such divergent immunologic effects on the host, the present study investigated lymphocytes that were isolated from the brains of Sindbis virus-infected animals. Cells from the brains of SJL mice exhibited more proliferation, produced more IL-2, maintained a higher viability, and expressed less bax mRNA (a proapoptotic mediator) than did lymphocytes from the brains of BALB/c mice. Since the central nervous system is enriched in gangliosides that regulate T cell proliferation and IL-2 production in vitro, purified brain-derived gangliosides were tested on peripheral lymphocytes from both strains. These lipids had less of an effect on the mitogen-induced proliferation, IL-2 production, activation-induced cell death, and up-regulation of bax mRNA in lymphocytes from SJL mice compared with those from BALB/c mice. Thus, gangliosides may inhibit various T cell effector functions and induce T cell apoptosis to a greater degree in the brains of BALB/c mice compared with the brains of SJL mice. This relative deficiency in local lymphocyte regulation may enhance the susceptibility of SJL mice to immune-mediated neurologic disease.