Neuroprotective effects of CD4+CD25+Foxp3+ regulatory T cells in a 3xTg-AD Alzheimer's disease model.
Neuroprotective effects of CD4+CD25+Foxp3+ regulatory T cells in a 3xTg-AD Alzheimer's disease model.
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DOI：
10.18632/oncotarget.12469
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发表时间：
2016-10-25
期刊：
影响因子：
--
通讯作者：
Bae H
中科院分区：
文献类型：
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作者：
Baek H;Ye M;Kang GH;Lee C;Lee G;Choi DB;Jung J;Kim H;Lee S;Kim JS;Lee HJ;Shim I;Lee JH;Bae H
阿尔茨海默病患者表现出神经病理学病变，包括淀粉样β（Aβ）肽的积累和神经纤维缠结。虽然引起神经退行性过程的机制在很大程度上是未知的，但越来越多的证据强调了免疫在阿尔茨海默病发病机制中的关键作用。在本研究中，我们研究了调节性T细胞（TCFs）在阿尔茨海默病进展中的作用。首先，我们探索了Tcells（CD 4 + CD 25 + T细胞）和Teffs（CD 4 + CD 25 − T细胞）在过继转移模型中的作用。将纯化的Tglutamine全身移植到3xTg-AD小鼠中可改善认知功能并减少Aβ斑块的沉积。相比之下，过继转移的Tefs减少行为功能和细胞因子的产生。接下来，我们使用抗CD 25抗体（PC61）瞬时耗尽Treg群体。四个月的Tglutamine耗尽导致六个月大的3xTg-AD小鼠的空间学习缺陷显著加重。此外，通过正电子发射断层扫描（PET）和18 F-2氟-2-脱氧-D-葡萄糖（[F-18] FDG）神经成像评估，它导致葡萄糖代谢降低。重要的是，与溶剂处理的3xTg-AD组相比，Treg耗尽的3xTg-AD的海马CA 1和CA 3区中Aβ斑块和小胶质细胞/巨噬细胞的沉积增加。我们的发现表明，全身性Treg给药可改善疾病进展，可能是一种有效的阿尔茨海默病治疗方法。
Alzheimer's disease patients display neuropathological lesions, including the accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles. Although the mechanisms causing the neurodegenerative process are largely unknown, increasing evidence highlights a critical role of immunity in the pathogenesis of Alzheimer's disease. In the present study, we investigated the role of regulatory T cells (Tregs) on Alzheimer's disease progression. First, we explored the effect of Tregs (CD4+CD25+ T cells) and Teffs (CD4+CD25− T cells) in an adoptive transfer model. Systemic transplantation of purified Tregs into 3xTg-AD mice improved cognitive function and reduced deposition of Aβ plaques. In contrast, adoptive transfer of Teffs diminished behavioral function and cytokine production. Next, we transiently depleted Treg population using an anti-CD25 antibody (PC61). Depletion of Tregs for four months resulted in a marked aggravation of the spatial learning deficits of six-month-old 3xTg-AD mice. Additionally, it resulted in decreasing glucose metabolism, as assessed by positron emission tomography (PET) with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) neuroimaging. Importantly, the deposition of Aβ plaques and microglia/macrophage was increased in the hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group. Our finding suggested that systemic Treg administration ameliorates disease progression and could be an effective Alzheimer's disease treatment.