Functional status of peripheral blood T-cells in ischemic stroke patients.

Functional status of peripheral blood T-cells in ischemic stroke patients.
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DOI:
10.1371/journal.pone.0008718
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发表时间:
2010-01-14
期刊:
影响因子:
3.7
通讯作者:
Dressel A
Dressel A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Vogelgesang A;May VE;Grunwald U;Bakkeboe M;Langner S;Wallaschofski H;Kessler C;Bröker BM;Dressel A

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在北半球,中风是致残的主要原因和主要的死亡原因。直到最近才有证据表明,脑缺血不仅会导致脑组织损伤和随后的局部炎症,而且还会在随后的感染中导致外周血T细胞的急剧丧失。然而,关于存活T细胞的激活状态的信息很少。因此,这项研究解决了中风引起的人类免疫学变化的功能后果。为此,我们分离了93例脑卒中患者外周血中的T细胞,并检测了其活化标志物的表达。此外,还采用了体外刺激试验来评估中风患者血液中T细胞的功能。与健康对照组相比,中风患者T细胞表面HLADR(p<0.0001)和CD25(pCTLA0.02)表达增强,提示中风导致T细胞活化,而 = -4仍未被检测到。体外研究表明,儿茶酚胺抑制活化的T细胞中CTLA-4的上调。在体外,中风患者的T细胞没有受到损害地增殖,并释放了更多的促炎细胞因子肿瘤坏死因子-α(p<0.01)和IL-6(p<0.05)。此外,中风患者血清中HMGB1浓度升高(p = 0.0002)。这些数据表明,卒中患者存活的T细胞仍具有完全的功能,并准备迎接TH1的应答,此外,我们还提供了证据表明,儿茶酚胺抑制CTLA-4的表达和血清HMGB1的释放可能是卒中诱导的T细胞活化的中介。
Stroke is a major cause of disability and leading cause of death in the northern hemisphere. Only recently it became evident that cerebral ischemia not only leads to brain tissue damage and subsequent local inflammation but also to a dramatic loss of peripheral blood T-cells with subsequent infections. However, only scarce information is available on the activation status of surviving T cells. This study therefore addressed the functional consequences of immunological changes induced by stroke in humans. For this purpose peripheral blood T-cells were isolated from 93 stroke patients and the expression of activation makers was determined. In addition ex vivo stimulation assays were applied to asses the functionality of T cells derived from blood of stroke patients. Compared to healthy controls, stroke patients demonstrated an enhanced surface expression of HLA-DR (p<0.0001) and CD25 (p = 0.02) on T cells, revealing that stroke leads to T cell activation, while CTLA-4 remained undetectable. In vitro studies revealed that catecholamines inhibit CTLA-4 upregulation in activated T cells. Ex vivo, T cells of stroke patients proliferated unimpaired and released increased amounts of the proinflammatory cytokine TNF-α (p<0.01) and IL-6 (p<0.05). Also, in sera of stroke patients HMGB1 concentrations were increased (p = 0.0002). The data demonstrate that surviving T cells in stroke patients remain fully functional and are primed towards a TH1 response, in addition we provide evidence that catecholamine mediated inhibition of CTLA-4 expression and serum HMGB1 release are possible mediators in stroke induced activation of T cells.
DOI: 10.1038/nature00858
发表时间: 2002-07-11
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