Brain-derived gangliosides regulate the cytokine production and proliferation of activated T cells.
Brain-derived gangliosides regulate the cytokine production and proliferation of activated T cells.
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DOI：
10.4049/jimmunol.157.10.4333
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发表时间：
1996-11
影响因子：
4.4
通讯作者：
David N. Irani;Kuo L. Lin;Diane E. Griffin
中科院分区：
文献类型：
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作者：
David N. Irani;Kuo L. Lin;Diane E. Griffin
神经节苷脂可以调节体内免疫系统的活性，特别是在它们最丰富的组织如肿瘤或中枢神经系统内。然而，神经节苷脂调节免疫功能的具体机制仍不完全清楚。我们已经表征了脑源性神经节苷脂对体外T细胞活化过程的特定步骤的影响。神经节苷脂抑制T细胞增殖下游的早期激活事件，绕过使用佛波酯加钙离子载体的组合。这些脂质可以阻断IL-2和IFN-γ基因转录，但不会抑制IL-4和IL-10 mRNA的产生。这可能是由于神经节苷脂能够阻止有丝分裂原刺激的T细胞中NF-κ B的活化。尽管抑制IL-2的产生，但神经节苷脂的抗增殖作用不会通过向培养基中添加补充的IL-2而逆转。这种缺陷持续存在，因为神经节苷脂也阻止活化的T细胞进入细胞周期。在这种情况下，视网膜母细胞瘤基因产物的磷酸化被阻止，该蛋白质的磷酸化状态是正常细胞周期进程的重要调节剂。这些研究有助于确定神经节苷脂如何在体外调节T细胞效应功能。他们还强调了这样一个事实，即某些T细胞反应，即Th 2相关细胞因子的产生，不受其作用的抑制。
Gangliosides may regulate the activity of the immune system in vivo, particularly within tissues such as neoplasms or the central nervous system, where they are most abundant. However, the specific mechanisms by which gangliosides modulate immune function remain incompletely understood. We have characterized the effects that brain-derived gangliosides have on specific steps of the T cell activation process in vitro. Gangliosides inhibit T cell proliferation downstream from the early activation events that are bypassed pharmacologically using the combination of a phorbol ester plus a calcium ionophore. These lipids block IL-2 and IFN-gamma gene transcription without inhibiting the production of IL-4 and IL-10 mRNA. This may be accounted for by the ability of gangliosides to prevent the activation of NF-kappaB in mitogen-stimulated T cells. Despite inhibiting IL-2 production, the antiproliferative effects of gangliosides are not reversed by adding supplemental IL-2 to the culture media. This defect persists because gangliosides also block the entry of activated T cells into the cell cycle. In this setting, phosphorylation of the retinoblastoma gene product, a protein whose phosphorylation state is an important regulator of normal cell cycle progression, is prevented. These studies help to define how gangliosides modulate T cell effector function in vitro. They also highlight the fact that certain T cell responses, namely the production of Th2-associated cytokines, are not inhibited by their actions.