包涵体肌炎血 T 和 NK 细胞的免疫表型分析。
Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells.
机构信息
Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA.
出版信息
Neurology. 2022 Mar 29;98(13):e1374-e1383. doi: 10.1212/WNL.0000000000200013. Epub 2022 Feb 7.
BACKGROUND AND OBJECTIVES
To evaluate the therapeutic potential of targeting highly differentiated T cells in patients with inclusion body myositis (IBM) by establishing high-resolution mapping of killer cell lectin-like receptor subfamily G member 1 (KLRG1) within the T and natural killer (NK) cell compartments.
METHODS
Blood was collected from 51 patients with IBM and 19 healthy age-matched donors. Peripheral blood mononuclear cells were interrogated by flow cytometry using a 12-marker antibody panel. The panel allowed the delineation of naive T cells (Tn), central memory T cells (Tcm), 4 stages of effector memory differentiation T cells (Tem 1-4), and effector memory re-expressing CD45RA T cells (TemRA), as well as total and subpopulations of NK cells based on the differential expression of CD16 and C56.
RESULTS
We found that a population of KLRG1 Tem and TemRA were expanded in both the CD4 and CD8 T-cell subpopulations in patients with IBM. KLRG1 expression in CD8 T cells increased with T-cell differentiation with the lowest levels of expression in Tn and highest in highly differentiated TemRA and CD56CD8 T cells. The frequency of KLRG1 total NK cells and subpopulations did not differ between patients with IBM and healthy donors. IBM disease duration correlated with increased CD8 T-cell differentiation.
DISCUSSION
Our findings reveal that the selective expansion of blood KLRG1 T cells in patients with IBM is confined to the TemRA and Tem cellular compartments.
背景与目的
通过建立杀伤细胞凝集素样受体亚家族 G 成员 1（KLRG1）在 T 细胞和自然杀伤（NK）细胞中的高分辨率图谱，评估针对包涵体肌炎（IBM）患者高度分化 T 细胞的治疗潜力。
方法
从 51 名 IBM 患者和 19 名年龄匹配的健康供体中采集血液。使用包含 12 种抗体的面板通过流式细胞术对外周血单核细胞进行检测。该面板允许根据 CD16 和 C56 的差异表达，对幼稚 T 细胞（Tn）、中央记忆 T 细胞（Tcm）、4 个效应记忆分化 T 细胞（Tem1-4）阶段和再表达 CD45RA 的效应记忆 T 细胞（TemRA）以及 NK 细胞的总群和亚群进行描绘。
结果
我们发现 IBM 患者的 CD4 和 CD8 T 细胞亚群中均扩增了 KLRG1 Tem 和 TemRA 群体。CD8 T 细胞中 KLRG1 的表达随着 T 细胞分化而增加，Tn 中的表达最低，高度分化的 TemRA 和 CD56CD8 T 细胞中的表达最高。IBM 患者和健康供体之间的总 NK 细胞和亚群的 KLRG1 频率没有差异。IBM 疾病持续时间与 CD8 T 细胞分化增加相关。
讨论
我们的研究结果表明，IBM 患者血液中 KLRG1 T 细胞的选择性扩增仅限于 TemRA 和 Tem 细胞区室。
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