Department of Immunology, University of Toronto, Toronto, Canada.
Department of Neurology, Yale School of Medicine, New Haven, United States.
Elife. 2019 Aug 1;8:e48051. doi: 10.7554/eLife.48051.
Multiple sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here, we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation. With post-acquisition analysis pipelines we were able to: (1) Discriminate demyelinating macrophages from the resident microglial pool; (2) Determine which types of lymphocytes reside closest to blood vessels; (3) Identify multiple subsets of T and B cells, and (4) Ascertain dynamics of T cell phenotypes vis-à-vis lesion type and location. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in MS patients.
多发性硬化症（MS）的特征是大脑和脊髓中出现脱髓鞘和炎症性病变，其细胞成分具有高度可变性。在这里，我们使用成像质谱细胞术（IMC）来实现对分期 MS 病变中 15 种以上蛋白质的同时成像。为了测试 IMC 区分不同类型病变的潜力，我们选择了一例在停用那他珠单抗后严重反弹的 MS 疾病活动的病例。通过采集后的分析流程，我们能够：（1）从常驻小胶质细胞池中区分脱髓鞘巨噬细胞；（2）确定哪种类型的淋巴细胞最接近血管；（3）鉴定多种 T 细胞和 B 细胞亚群；以及（4）确定 T 细胞表型与病变类型和位置的动态关系。我们提出，IMC 将能够全面分析单细胞表型、它们的功能状态和细胞-细胞相互作用，以及 MS 患者病变形态计量学和脱髓鞘活性的关系。
