Communication of CD8+ T cells with mononuclear phagocytes in multiple sclerosis
Communication of CD8+ T cells with mononuclear phagocytes in multiple sclerosis
复制标题
多发性硬化症中 CD8 T 细胞与单核吞噬细胞的通讯
DOI：
10.1002/acn3.783
复制
发表时间：
2019
影响因子：
5.3
通讯作者：
Dornmair
中科院分区：
文献类型：
--
作者：
Konjevic-Sabolek;Beltrán;Hohlfeld;Lassmann;Dornmair
目的CD8+T细胞是多发性硬化(MS)患者炎性病变中最常见的淋巴细胞，但目前尚不清楚它们是被动的旁观者，还是与脑内其他细胞的主动交流。为了确定它们潜在的相互作用伙伴，我们分析了含有矢量定向的细胞毒颗粒的CD8+T细胞，并分析了颗粒指向的区域。方法对1例抗CD8抗体和穿孔素抗体阳性的MS活动性皮损进行冰冻切片染色，寻找矢量定向的穿孔素颗粒，并通过激光显微解剖分离与颗粒相对的靶区和对照区域。从这两个方面，我们通过下一代测序分析了细胞类型的特定转录本。结果发现单核巨噬细胞(MP)特异性标记物CD163和CD11b仅在显微切割的靶区表达，而在对照区域未见表达。我们用经典的免疫组织化学方法验证了MPS是CD8+T细胞在MS病变中的通讯伙伴的发现，该发现来自标记型患者和其他急进性MS和其他炎症性神经系统疾病患者。尽管目前尚不清楚这些相互作用是否导致CD8+T细胞杀死沟通伙伴，但我们的数据强调CD8+T细胞在MS的发病机制中发挥着积极的作用。
ObjectiveCD8+T cells are the most prevailing lymphocyte population in inflammatory lesions of patients with multiple sclerosis (MS) but it is not even known whether they are merely passive bystanders or actively communicate with other cells in the brain. To identify their potential interaction partners, we analyzed CD8+T cells that contained vectorially oriented cytotoxic granules and analyzed the areas to which the granules pointed.MethodsWe stained cryo‐sections of active MS lesions of an index patient with antibodies to CD8 and perforin, searched for vectorially oriented perforin granules, and isolated target areas opposing the granules and control areas by laser‐microdissection. From both areas, we analyzed cell‐type specific transcripts by next‐generation sequencing. In parallel, we stained samples from the index‐patient and other patients by four‐color immunohistochemistry (IHC).ResultsWe found transcripts of the mononuclear phagocyte (MP) specific markers CD163 and CD11b only in the microdissected target areas but not in control areas. We validated the finding that MPs are communication partners of CD8+T cells in MS lesions by classical IHC in samples from the index‐patient and other patients with acute and progressive MS and other inflammatory neurological diseases.InterpretationBecause CD163 and CD11b are specifically expressed in MPs, our findings suggest that CD8+T cells communicate with local MPs. Although it is still unclear if these interactions lead to killing of the communication partners by CD8+T cells, our data underline that CD8+T cells play an active role in the pathogenesis of MS.
登录
查看更多内容
影响因子：
46.9
作者：
Han, Arnold;Glanville, Jacob;Hansmann, Leo;Davis, Mark M.
通讯作者：
Davis, Mark M.
来自多发性硬化症脑病变的αβT细胞受体显示与MAIT细胞相关的特征。
DOI：
10.1212/nxi.0000000000000107
发表时间：
2015-08
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
--
作者：
Held K;Bhonsle-Deeng L;Siewert K;Sato W;Beltrán E;Schmidt S;Rühl G;Ng JK;Engerer P;Moser M;Klinkert WE;Babbe H;Misgeld T;Wekerle H;Laplaud DA;Hohlfeld R;Dornmair K
通讯作者：
Dornmair K
影响因子：
32.4
作者：
Halle S;Keyser KA;Stahl FR;Busche A;Marquardt A;Zheng X;Galla M;Heissmeyer V;Heller K;Boelter J;Wagner K;Bischoff Y;Martens R;Braun A;Werth K;Uvarovskii A;Kempf H;Meyer-Hermann M;Arens R;Kremer M;Sutter G;Messerle M;Förster R
通讯作者：
Förster R
DOI：
10.1073/pnas.1519608113
发表时间：
2016-03-22
影响因子：
11.1
作者：
Flach, Anne-Christine;Litke, Tanja;Fluegel, Alexander
通讯作者：
Fluegel, Alexander
影响因子：
25
作者：
Locatelli, Giuseppe;Theodorou, Delphine;Kerschensteiner, Martin
通讯作者：
Kerschensteiner, Martin