Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells
Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells
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DOI：
10.1212/wnl.0000000000200013
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发表时间：
2022-03-29
期刊：
影响因子：
9.9
通讯作者：
Villalta, S. Armando
中科院分区：
文献类型：
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作者：
Goyal, Namita A.;Coulis, Gerald;Villalta, S. Armando
背景和目的 通过建立 T 细胞和自然杀伤 (NK) 细胞区室中杀伤细胞凝集素样受体亚家族 G 成员 1 (KLRG1(+)) 的高分辨率图谱，评估针对包涵体肌炎 (IBM) 患者的高度分化 T 细胞的治疗潜力。方法 采集 51 名 IBM 患者和 19 名年龄匹配的健康献血者的血液。使用 12 标记抗体组通过流式细胞术检测外周血单核细胞。该面板允许描绘初始 T 细胞 (Tn)、中央记忆 T 细胞 (Tcm)、4 个阶段的效应记忆分化 T 细胞 (Tem 1-4) 和效应记忆重新表达 CD45RA T 细胞 (TemRA)，以及基于 CD16 和 C56 差异表达的 NK 细胞总数和亚群。结果我们发现 IBM 患者的 CD4(+) 和 CD8(+) T 细胞亚群中 KLRG1(+) Tem 和 TemRA 的数量均有所增加。 CD8(+)T细胞中KLRG1的表达随着T细胞分化而增加，其中Tn中表达水平最低，而在高度分化的TemRA和CD56(+)CD8(+)T细胞中表达水平最高。 IBM 患者和健康供体之间 KLRG1(+) 总 NK 细胞和亚群的频率没有差异。 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 KLRG1(+) T 细胞的选择性扩增仅限于 TemRA 和 Tem 细胞区室。
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 CD56(+)CD8(+) 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.