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首页> 外文期刊>The European Journal of Neuroscience >Low-dose gamma-irradiation promotes survival of injured neurons in the central nervous system via homeostasis-driven proliferation of T cells.
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Low-dose gamma-irradiation promotes survival of injured neurons in the central nervous system via homeostasis-driven proliferation of T cells.

机译:小剂量伽马射线辐射通过稳态驱动的T细胞增殖促进中枢神经系统中受损神经元的存活。

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摘要

Abstract Protective autoimmunity was only recently recognized as a mechanism for attenuating the progression of neurodegeneration. Using a rat model of optic nerve crush or contusive spinal cord injury, and a mouse model of neurodegenerative conditions caused by injection of a toxic dose of intraocular glutamate, we show that a single low dose of whole-body or lymphoid-organ gamma-irradiation significantly improved the spontaneous recovery. Animals with severe immune deficiency or deprived of mature T cells were unable to benefit from this treatment, suggesting that the irradiation-induced neuroprotection is immune mediated. This suggestion received further support from the findings that irradiation was accompanied by an increased incidence of activated T cells in the lymphoid organs and peripheral blood and an increase in mRNA encoding for the pro-inflammatory cytokines interleukin-12 and interferon-gamma, and that after irradiation, passive transfer of a subpopulation of suppressive T cells (naturally occurring regulatory CD4(+)CD25(+) T cells) wiped out the irradiation-induced protection. These results suggest that homeostasis-driven proliferation of T cells, induced by a single low-dose irradiation, leads to boosting of T cell-mediated neuroprotection and can be utilized clinically to fight off neurodegeneration and the threat of other diseases in which defense against toxic self-compounds is needed.
机译:摘要保护性自身免疫只是最近才被认为是减轻神经退行性疾病进展的一种机制。使用视神经挤压或挫伤性脊髓损伤的大鼠模型,以及注射有毒剂量的眼内谷氨酸引起的神经退行性疾病的小鼠模型,我们证明了单个低剂量的全身或淋巴器官γ射线照射显着提高了自发恢复能力。具有严重免疫缺陷或缺乏成熟T细胞的动物无法从这种治疗中受益,这表明辐射诱导的神经保护作用是免疫介导的。这一发现得到了进一步的支持,这一发现表明,辐射伴随着淋巴器官和外周血中活化T细胞的发生率增加以及编码促炎性细胞因子白细胞介素12和干扰素-γ的mRNA的增加。辐射,抑制性T细胞(自然发生的调节性CD4(+)CD25(+)T细胞)亚群的被动转移消除了辐射诱导的保护作用。这些结果表明,由单次低剂量照射诱导的稳态驱动的T细胞增殖可导致T细胞介导的神经保护作用增强,并可在临床上用于抵抗神经退行性变以及其他抵抗毒性反应的疾病的威胁。需要自我化合物。

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