Low-dose γ-irradiation promotes survival of injured neurons in the central nervous system via homeostasis-driven proliferation of T cells
Low-dose γ-irradiation promotes survival of injured neurons in the central nervous system via homeostasis-driven proliferation of T cells
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DOI：
10.1111/j.1460-9568.2004.03207.x
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发表时间：
2004-03-01
影响因子：
3.4
通讯作者：
Schwartz, M
中科院分区：
文献类型：
--
作者：
Kipnis, J;Avidan, H;Schwartz, M
保护性自身免疫直到最近才被认为是一种减缓神经退行性疾病进展的机制。通过对视神经损伤或脊髓挫伤大鼠模型和眼内注射有毒剂量谷氨酸引起的神经退行性疾病小鼠模型的研究，我们发现单次低剂量的全身或淋巴器官γ照射可显著改善自发恢复。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获益，这表明辐射诱导的神经保护是免疫介导的。这一观点得到了以下研究结果的进一步支持：辐照伴随着淋巴器官和外周血中活化T细胞的增加，以及编码促炎细胞因子白介素-12和干扰素- γ的mRNA的增加，并且辐照后，抑制性T细胞亚群(自然发生的调节性CD4（+)CD25(+) T细胞）的被动转移消除了辐照诱导的保护作用。这些结果表明，单次低剂量照射诱导的内稳态驱动的T细胞增殖，导致T细胞介导的神经保护增强，可以在临床上用于抵抗神经退行性变和其他需要防御有毒自身化合物的疾病的威胁。
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.