Intracerebral human regulatory T cells: analysis of CD4+ CD25+ FOXP3+ T cells in brain lesions and cerebrospinal fluid of multiple sclerosis patients.
Intracerebral human regulatory T cells: analysis of CD4+ CD25+ FOXP3+ T cells in brain lesions and cerebrospinal fluid of multiple sclerosis patients.
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DOI：
10.1371/journal.pone.0017988
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发表时间：
2011-03-18
期刊：
影响因子：
3.7
通讯作者：
Wildemann B
中科院分区：
文献类型：
--
作者：
Fritzsching B;Haas J;König F;Kunz P;Fritzsching E;Pöschl J;Krammer PH;Brück W;Suri-Payer E;Wildemann B
多个实验室已经报道了多发性硬化症（MS）患者外周血中CD4+CD25+FOXP3+调节性T细胞（Treg）抑制能力受损。然而，由于大多数研究只分析了外周血样本，目前尚不清楚MS患者的Treg功能障碍是否仅限于外周T细胞活化控制的降低。在这里，我们通过FOXP3免疫组织化学评估了16例MS患者的早期活动性MS病变。此外，我们使用六色流式细胞术通过分析17例treatment-naïve MS患者外周血和脑脊液中FOXP3/CD127的表达以及循环和脑脊液中凋亡敏感的CD45ROhiCD95hi细胞的数量来确定Treg的数量。MS脑病变中FOXP3+和CD4+细胞的绝对数量相当低，尽管存在CD4+细胞浸润，但在30%的MS活检中未检测到Treg。相比之下，在所有脑脊液样本中均可检测到Treg，并且与MS患者的外周血相比，发现具有CD45ROhiCD95hi表型的Treg在脑脊液中富集，之前被证明对细胞凋亡高度敏感。我们提出了一种假设的模型，即通过cd95l介导的MS病变内的细胞凋亡在脑内消除Treg。
Impaired suppressive capacity of CD4+CD25+FOXP3+ regulatory T cells (Treg) from peripheral blood of patients with multiple sclerosis (MS) has been reported by multiple laboratories. It is, however, currently unresolved whether Treg dysfunction in MS patients is limited to reduced control of peripheral T cell activation since most studies analyzed peripheral blood samples only. Here, we assessed early active MS lesions in brain biopsies obtained from 16 patients with MS by FOXP3 immunohistochemistry. In addition, we used six-color flow cytometry to determine numbers of Treg by analysis of FOXP3/CD127 expression in peripheral blood and cerebrospinal fluid (CSF) of 17 treatment-naïve MS patients as well as quantities of apoptosis sensitive CD45ROhiCD95hi cells in circulating and CSF Treg subsets. Absolute numbers of FOXP3+ and CD4+ cells were rather low in MS brain lesions and Treg were not detectable in 30% of MS biopsies despite the presence of CD4+ cell infiltrates. In contrast, Treg were detectable in all CSF samples and Treg with a CD45ROhiCD95hi phenotype previously shown to be highly apoptosis sensitive were found to be enriched in the CSF compared to peripheral blood of MS patients. We suggest a hypothetical model of intracerebral elimination of Treg by CD95L-mediated apoptosis within the MS lesion.