Espinosa-Ortega F, Gómez-Martin D, Santana-De Anda K, Romo-Tena J, Villaseñor-Ovies P, Alcocer-Varela J
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico.
Clin Exp Immunol. 2015 Mar;179(3):520-8. doi: 10.1111/cei.12475.
The role of T cells in idiopathic inflammatory myopathies (IIM) is not yet clear. Some alterations in certain subsets have been reported in inflamed muscle cells. However, a broad quantitative assessment of peripheral T cell subsets has not been evaluated. The aim of this study was to address the quantitative profile of potential pathogenic T cell subsets, namely follicular helper T cells (Tfh), T helper type 17 (Th17), CD28(null) and regulatory T cells (Tregs ) in peripheral blood from IIM patients. Thirty IIM patients and 30 age- and gender-matched healthy donors were included. Peripheral blood mononuclear cells were isolated. T cell subsets were evaluated by flow cytometry, as follows: Tfh (CD4(+) CXCR5(+) ) and its subsets Tfh1 (CXCR3(+) CCR6(-) ), Tfh2 (CXCR3(-) CCR6(-) ), Tfh17 (CXCR3(-) CCR6(+) ), Th17 (CD4(+) IL17A(+) ), CD28(null) (CD4(+) CD28(-) CD244(+) ) and Tregs (CD4(+) CD25(high) forkhead box protein 3 (FoxP3(+) ); CD8(+) CD25(high) FoxP3(+) ). Percentage, absolute numbers and mean fluorescence intensity were analysed. We found increased numbers of total Tfh cells (28 ± 8.16 versus 6.64 ± 1.29, P=0.031) in IIM patients when compared to healthy controls. Moreover, this increment was dependent upon Tfh2 and Tfh17 (Tfh2:9.49 ± 2.19 versus 1.66 ± 0.46, P=0.005; Tfh17 9.48 ± 2.83 versus 1.18 ± 0.21, P=0.014). Also, IIM patients showed higher numbers of Th17 cells (30.25 ± 6.49 versus 13.46 ± 2.95, P=0.031) as well as decreased number of Tregs (5.98 ± 1.61 versus 30.82 ± 8.38, P=0.009). We also found an expansion of CD28(null) cells (162.88 ± 32.29 versus 64 ± 17.35, P=0.015). Our data suggest that IIM patients are characterized by an expansion of peripheral proinflammatory T cells, such as Tfh and Th17, as well as pro-apoptotic CD28 null cells and a deficiency of suppressor populations of Tregs (CD4(+) and CD8(+) ).
T细胞在特发性炎性肌病（IIM）中的作用尚不清楚。在发炎的肌肉细胞中已报道了某些亚群的一些改变。然而，尚未对外周血T细胞亚群进行广泛的定量评估。本研究的目的是探讨IIM患者外周血中潜在致病性T细胞亚群的定量特征，即滤泡辅助性T细胞（Tfh）、17型辅助性T细胞（Th17）、CD28阴性细胞和调节性T细胞（Tregs）。纳入了30例IIM患者和30例年龄及性别匹配的健康供体。分离外周血单个核细胞。通过流式细胞术评估T细胞亚群，具体如下：Tfh（CD4(+) CXCR5(+)）及其亚群Tfh1（CXCR3(+) CCR6(-)）、Tfh2（CXCR3(-) CCR6(-)）、Tfh17（CXCR3(-) CCR6(+)）、Th17（CD4(+) IL17A(+)）、CD28阴性细胞（CD4(+) CD28(-) CD244(+)）和Tregs（CD4(+) CD25(高) 叉头框蛋白3（FoxP3(+)）；CD8(+) CD25(高) FoxP3(+)）。分析百分比、绝对数量和平均荧光强度。我们发现，与健康对照相比，IIM患者的总Tfh细胞数量增加（28±8.16对6.64±1.29，P=0.031）。此外，这种增加依赖于Tfh2和Tfh17（Tfh2：9.49±2.19对1.66±0.46，P=0.005；Tfh17 9.48±2.83对1.18±0.21，P=0.014）。此外，IIM患者的Th17细胞数量也更高（30.25±6.49对13.46±2.95，P=0.031），而Tregs数量减少（5.98±1.61对30.82±8.38，P=0.009）。我们还发现CD28阴性细胞有所扩增（162.88±32.29对64±17.35，P=0.015）。我们的数据表明，IIM患者的特征是外周促炎性T细胞（如Tfh和Th17）以及促凋亡的CD28阴性细胞扩增，而Tregs（CD4(+)和CD8(+)）抑制性群体缺乏。
