Hsiao Cheng-Chih, Engelenburg Hendrik J, Jongejan Aldo, Zhu Jing, Zhang Baohong, Mingueneau Michael, Moerland Perry D, Huitinga Inge, Smolders Joost, Hamann Jörg
Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands.
Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, 1105 AZ Amsterdam, the Netherlands.
iScience. 2022 Dec 9;26(1):105785. doi: 10.1016/j.isci.2022.105785. eCollection 2023 Jan 20.
The human brain is populated by perivascular T cells with a tissue-resident memory T (T)-cell phenotype, which in multiple sclerosis (MS) associate with lesions. We investigated the transcriptional and functional profile of freshly isolated T cells from white and gray matter. RNA sequencing of CD8 and CD4 CD69 T cells revealed T-cell signatures. Notably, gene expression hardly differed between lesional and normal-appearing white matter T cells in MS brains. Genes up-regulated in brain T cells were (CD20) and (osteopontin, OPN). OPN is also abundantly expressed by microglia and has been shown to inhibit T cell activity. In line with their parenchymal localization and the increased presence of OPN in active MS lesions, we noticed a reduced production of inflammatory cytokines IL-2, TNF, and IFNγ by lesion-derived CD8 and CD4 T cells . Our study reports traits of brain T cells and reveals their tight control in MS lesions.
人脑中存在具有组织驻留记忆T（TRM）细胞表型的血管周围T细胞，在多发性硬化症（MS）中，这些细胞与病变相关。我们研究了从白质和灰质中新鲜分离的T细胞的转录和功能特征。对CD8和CD4 CD69 T细胞进行RNA测序，揭示了T细胞特征。值得注意的是，MS脑内病变白质T细胞和外观正常白质T细胞之间的基因表达几乎没有差异。脑T细胞中上调的基因是（CD20）和（骨桥蛋白，OPN）。OPN在小胶质细胞中也大量表达，并且已被证明可抑制T细胞活性。鉴于它们在实质中的定位以及OPN在活动性MS病变中的增加，我们注意到病变来源的CD8和CD4 T细胞产生的炎性细胞因子IL-2、TNF和IFNγ减少。我们的研究报告了脑T细胞的特征，并揭示了它们在MS病变中受到的严格调控。
