Pro-inflammatory T-lymphocytes rapidly infiltrate into the brain and contribute to neuronal injury following cardiac arrest and cardiopulmonary resuscitation
Pro-inflammatory T-lymphocytes rapidly infiltrate into the brain and contribute to neuronal injury following cardiac arrest and cardiopulmonary resuscitation
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DOI：
10.1016/j.jneuroim.2014.07.009
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发表时间：
2014-09-15
影响因子：
3.3
通讯作者：
Herson, Paco S.
中科院分区：
文献类型：
--
作者：
Deng, Guiying;Carter, Jessica;Herson, Paco S.
虽然炎症机制与全脑缺血后的神经元损伤有关，但浸润性外周免疫细胞的存在仍未得到充分研究。我们进行流式细胞术的单细胞悬浮液从小鼠脑中获得在不同的时间点后，全脑缺血心脏骤停和心肺复苏（CA/CPR）诱导的特征流入受损的大脑淋巴细胞。我们观察到CA/CPR在复苏后3小时内引起大量淋巴细胞流入，并在我们实验的3天持续时间内保持。细胞染色流式细胞术观察到绝大多数浸润淋巴细胞为CD 4（+）T细胞。细胞内染色显示大比例的促炎性T细胞表达TNF α或INF γ。重要的是，TCR α敲除小鼠中功能性T细胞的缺乏减少了CA/CPR后的神经元损伤，这暗示促炎性T细胞参与了缺血性神经元损伤的进展。最后，我们进行了显著的观察，即与自身免疫强烈相关的新型CD 4（+）CD 40（+）（Th 40）促炎性T细胞群体大量存在于受损的大脑中。这些数据表明，研究全脑缺血后的神经免疫反应应考虑浸润T细胞在协调急性和持续的免疫反应的作用。(C)2014爱思唯尔有限公司版权所有。
Although inflammatory mechanisms have been linked to neuronal injury following global cerebral ischemia, the presence of infiltrating peripheral immune cells remains understudied. We performed flow cytometry of single cell suspensions obtained from the brains of mice at varying time points after global cerebral ischemia induced by cardiac arrest and cardiopulmonary resuscitation (CA/CPR) to characterize the influx of lymphocytes into the injured brain. We observed that CA/CPR caused a large influx of lymphocytes within 3 h of resuscitation that was maintained for the 3 day duration of our experiments. Using cell staining flow cytometry we observed that the large majority of infiltrating lymphocytes were CD4(+)T cells. Intracellular stains revealed a large proportion of pro-inflammatory T cells expressing either TNF alpha or INF gamma. Importantly, the lack of functional T cells in TCR alpha knockout mice reduced neuronal injury following CA/CPR, implicating pro-inflammatory T cells in the progression of ischemic neuronal injury. Finally, we made the remarkable observation that the novel CD4(+)CD40(+) (Th40) population of pro-inflammatory T cells that are strongly associated with autoimmunity are present in large numbers in the injured brain. These data indicate that studies investigating the neuro-immune response after global cerebral ischemia should consider the role of infiltrating T cells in orchestrating the acute and sustained immune response. (C) 2014 Elsevier B.V. All rights reserved.