Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis.
Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis.
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DOI：
10.1002/acn3.199
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发表时间：
2015-06
影响因子：
5.3
通讯作者：
Laplaud, David A.
中科院分区：
文献类型：
--
作者：
Salou, Marion;Garcia, Alexandra;Michel, Laure;Gainche-Salmon, Anne;Loussouarn, Delphine;Nicol, Bryan;Guillot, Flora;Hulin, Philippe;Nedellec, Steven;Baron, Daniel;Ramstein, Gerard;Soulillou, Jean-Paul;Brouard, Sophie;Nicot, Arnaud B.;Degauque, Nicolas;Laplaud, David A.
在多发性硬化症（MS）、中枢神经系统（CNS）、脑脊液（CSF）和血液中显示CD8+ T细胞的TCR克隆扩增。这些克隆体被假设——但从未被证明——在三个隔间中是相似的。解决这个关键问题对于推断外周克隆扩增的CD8+ T细胞在该疾病中的意义至关重要。首次使用互补确定区3 （CDR3）光谱分型和高通量测序研究了来自3例MS患者的配对血液（纯化的CD8+和CD4+ T细胞）、CSF和CNS（22个病变，各种炎症和脱髓鞘状态）样本的TCR Vβ库。同时，用荧光染色对血液和中枢神经系统克隆扩增的CD8+ T细胞进行表征。TCR Vβ库分析显示，CNS病变、CSF和血液CD8+ T细胞之间的优势T细胞克隆具有很强的共享性。与此同时，我们发现血液低克隆CD8+ T细胞表现出致病细胞的特征，因为它们在MS患者中表现出对记忆表型的偏见，与非低克隆对照物相比，CCR5、CD11a和颗粒酶B （GZM-B）的表达增加。cns浸润T细胞主要表达CD11a和GZM-B。这项研究强调了CD8+ T细胞在MS病理生理中的主要意义，并表明潜在的侵袭性CD8+ T细胞可以很容易地从血液和脑脊液样本中识别和表征。
In multiple sclerosis (MS), central nervous system (CNS), cerebrospinal fluid (CSF), and blood display TCR clonal expansions of CD8+ T cells. These clones have been assumed – but never demonstrated – to be similar in the three compartments. Addressing this key question is essential to infer the implication of peripheral clonally expanded CD8+ T cells in the disease. For the first time, TCR Vβ repertoire from paired blood (purified CD8+ and CD4+ T cells), CSF and CNS (22 lesions, various inflammatory and demyelination statuses) samples from three MS patients was studied using complementary determining region 3 (CDR3) spectratyping and high-throughput sequencing. In parallel, blood and CNS clonally expanded CD8+ T cells were characterized by fluorescent staining. TCR Vβ repertoire analysis revealed strong sharing of predominant T-cell clones between CNS lesions, CSF, and blood CD8+ T cells. In parallel, we showed that blood oligoclonal CD8+ T cells exhibit characteristics of pathogenic cells, as they displayed a bias toward a memory phenotype in MS patients, with increased expression of CCR5, CD11a and Granzyme B (GZM-B) compared to non oligoclonal counterparts. CNS-infiltrating T cells were mainly CD8 expressing CD11a and GZM-B. This study highlights the predominant implication of CD8+ T cells in MS pathophysiology and demonstrates that potentially aggressive CD8+ T cells can be easily identified and characterized from blood and CSF samples.
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影响因子：
5.5
作者：
Giunti, D;Borsellino, G;Uccelli, A
通讯作者：
Uccelli, A
影响因子：
11
作者：
Gestri, D;Baldacci, L;Massacesi, L
通讯作者：
Massacesi, L
影响因子：
11.2
作者：
HAUSER, SL;BHAN, AK;WEINER, HL
通讯作者：
WEINER, HL
影响因子：
8.6
作者：
Jilek, Samantha;Schluep, Myriam;Du Pasquier, Renaud A.
通讯作者：
Du Pasquier, Renaud A.
DOI：
10.1084/jem.192.3.393
发表时间：
2000-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Babbe H;Roers A;Waisman A;Lassmann H;Goebels N;Hohlfeld R;Friese M;Schröder R;Deckert M;Schmidt S;Ravid R;Rajewsky K
通讯作者：
Rajewsky K