Abeta-specific Th2 cells provide cognitive and pathological benefits to Alzheimer's mice without infiltrating the CNS.

Abeta-specific Th2 cells provide cognitive and pathological benefits to Alzheimer's mice without infiltrating the CNS.
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DOI:
10.1016/j.nbd.2008.12.015
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发表时间:
2009-04
影响因子:
6.1
通讯作者:
Ethell DW
Ethell DW
中科院分区:
医学1区
文献类型:
--
作者:
Cao C;Arendash GW;Dickson A;Mamcarz MB;Lin X;Ethell DW

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我们发现,少量纯化的Th 2偏向Aβ特异性T细胞足以在阿尔茨海默病的APP+PS1小鼠模型中提供深远的认知和病理益处。接受T细胞输注6周后,认知受损小鼠在工作记忆任务中表现明显更好,这与可溶性Aβ的较高血浆水平相关。海马的病理学分析显示,在T细胞处理的小鼠中,斑块相关的小胶质细胞减少30%,血管淀粉样变性减少。Aβ特异性Th 2细胞的输注还降低了IFN-γ、TNF-α、GM-CSF、IL-2和IL-4的血浆水平,这些水平在未处理的APP+PS1小鼠中升高。在T细胞处理的小鼠中没有发生显著的免疫细胞浸润和抗Abeta抗体滴度。这些结果表明,Aβ特异性Th 2细胞足以逆转认知障碍,并在阿尔茨海默氏症小鼠模型中提供多种病理学益处。
We have found that a small number of purified Th2-biased Aβ-specific T cells are sufficient to provide profound cognitive and pathological benefits in an APP+PS1 mouse model for Alzheimer’s disease. Six weeks after receiving T cell infusions, cognitively-impaired mice performed significantly better in working memory tasks, which correlated with higher plasma levels of soluble Aβ. Pathological analysis of the hippocampus revealed a 30% decrease of plaque- associated microglia and less vascular amyloidosis in T cell treated mice. The infusion of Aβ-specific Th2 cells also reduced plasma levels of IFN-γ, TNF-α, GM-CSF, IL-2 and IL-4, which are elevated in untreated APP+PS1 mice. No significant immune cell infiltration and no anti-Abeta antibody titers occurred in the T cell treated mice. These results demonstrate that Aβ-specific Th2 cells are sufficient to reverse cognitive impairment and provide multiple pathological benefits in an Alzheimer’s mouse model.
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