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多发性硬化症患者自体造血干细胞移植后自然杀伤细胞和先天样 T 细胞。

NK Cells and Innate-Like T Cells After Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis.

机构信息

Neuroimmunology and Multiple Sclerosis (MS) Research Section (NIMS), Department of Neurology, University and University Hospital Zurich, Zurich, Switzerland.

Department of Medical Oncology and Hematology, University and University Hospital Zurich, Zurich, Switzerland.

出版信息

Front Immunol. 2021 Dec 16;12:794077. doi: 10.3389/fimmu.2021.794077. eCollection 2021.

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which autoreactive T and B cells play important roles. Other lymphocytes such as NK cells and innate-like T cells appear to be involved as well. To name a few examples, CD56 NK cells were described as an immunoregulatory NK cell subset in MS while innate-like T cells in MS were described in brain lesions and with proinflammatory signatures. Autologous hematopoietic stem cell transplantation (aHSCT) is a procedure used to treat MS. This procedure includes hematopoietic stem/progenitor cell (HSPC) mobilization, then high-dose chemotherapy combined with anti-thymocyte globulin (ATG) and subsequent infusion of the patients own HSPCs to reconstitute a functional immune system. aHSCT inhibits MS disease activity very effectively and for long time, presumably due to elimination of autoreactive T cells. Here, we performed multidimensional flow cytometry experiments in peripheral blood lymphocytes of 27 MS patients before and after aHSCT to address its potential influence on NK and innate-like T cells. After aHSCT, the relative frequency and absolute numbers of CD56 NK cells rise above pre-aHSCT levels while all studied innate-like T cell populations decrease. Hence, our data support an enhanced immune regulation by CD56 NK cells and the efficient reduction of proinflammatory innate-like T cells by aHSCT in MS. These observations contribute to our current understanding of the immunological effects of aHSCT in MS.

摘要

多发性硬化症(MS)是一种中枢神经系统自身免疫性疾病,其中自身反应性 T 和 B 细胞起着重要作用。其他淋巴细胞,如 NK 细胞和先天样 T 细胞,似乎也参与其中。例如,CD56 NK 细胞被描述为 MS 中的一种免疫调节性 NK 细胞亚群,而 MS 中的先天样 T 细胞则在脑损伤中被描述,并具有促炎特征。自体造血干细胞移植(aHSCT)是一种用于治疗 MS 的程序。该程序包括造血干细胞/祖细胞(HSPC)动员,然后用高剂量化疗联合抗胸腺细胞球蛋白(ATG),随后输注患者自身的 HSPC 以重建功能性免疫系统。aHSCT 非常有效地抑制 MS 疾病活动,并且持续时间长,可能是由于清除了自身反应性 T 细胞。在这里,我们在 27 例 MS 患者接受 aHSCT 前后进行了外周血淋巴细胞的多维流式细胞术实验,以探讨其对 NK 和先天样 T 细胞的潜在影响。在 aHSCT 后,CD56 NK 细胞的相对频率和绝对数量升高,超过 aHSCT 前的水平,而所有研究的先天样 T 细胞群均减少。因此,我们的数据支持 CD56 NK 细胞增强免疫调节和 aHSCT 有效减少 MS 中的促炎先天样 T 细胞。这些观察结果有助于我们目前对 aHSCT 在 MS 中的免疫学影响的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942d/8716406/168cc4922eb2/fimmu-12-794077-g001.jpg

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