Characterization of Effector Memory CD8+ T Cells in the Synovial Fluid of Rheumatoid Arthritis
Characterization of Effector Memory CD8+ T Cells in the Synovial Fluid of Rheumatoid Arthritis
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DOI：
10.1007/s10875-012-9674-3
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发表时间：
2012-08-01
影响因子：
9.1
通讯作者：
Kim, Hang-Rae
中科院分区：
文献类型：
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作者：
Cho, Bon-A;Sim, Ji Hyun;Kim, Hang-Rae
对于类风湿性关节炎（RA）中CD8(+) T细胞的细胞特性知之甚少。我们通过研究RA患者外周血和滑液（SF）中CD8(+) T细胞亚群的频率及其表型特征是否发生改变来解决这一问题。在本研究中，与健康对照相比，RA患者SF中CD8(+) T细胞，主要是CD45RA（-）效应记忆（EM） CD8(+) T细胞显著增加，而外周血中CD8(+) T细胞则没有显著增加。滑膜EM CD8(+) T细胞具有高水平CD80、CD86和PD-1的活化表型，Ki-67染色显示其在体内具有增殖特征，而fas阳性细胞则倾向于凋亡。此外，SF中的EM CD8(+) T细胞的细胞毒性较低，因为它们表达的穿孔素和颗粒酶b较少。特别是，滑膜液中CCR4(+)CD8(+) T细胞和产生il -4的CD8(+) T细胞（即Tc2细胞）的比例显著高于RA患者和健康对照的外周血单个核细胞。此外，RA患者SF中产生il -10的CD8（+）抑制T (T)细胞数量显著增加。特别是，CD8(+) T细胞与疾病活动性呈负相关。这些发现强烈提示，SF中的EM CD8(+) T细胞增加，可能与炎症有关，它们可能参与调节炎症，从而影响RA的发生和进展。
Little is known about the cellular characteristics of CD8(+) T cells in rheumatoid arthritis (RA). We addressed this by investigating whether the frequency of the CD8(+) T cell subsets and their phenotypic characteristics are altered in the peripheral blood and synovial fluid (SF) from patients with RA. In this study, CD8(+) T cells, mainly CD45RA(-) effector memory (EM) CD8(+) T cells, were increased significantly in the SF, but not in the peripheral blood from RA patients, compared with healthy controls. The synovial EM CD8(+) T cells were activated phenotypes with high levels of CD80, CD86, and PD-1, and had a proliferating signature in vivo upon Ki-67 staining, whereas the Fas-positive cells were prone to apoptosis. In addition, EM CD8(+) T cells in the SF were less cytotoxic, as they expressed less perforin and granzyme B. In particular, the proportions of synovial fluid mononuclear cells that were CCR4(+)CD8(+) T cells and IL-4-producing CD8(+) T cells (i.e., Tc2 cells) were significantly higher than those in peripheral blood mononuclear cells of patients with RA and healthy controls. In addition, the number of IL-10-producing CD8(+) suppressor T (Ts) cells increased significantly in the SF of RA patients. Especially, CD8(+) T cells were inversely correlated with disease activity. These findings strongly suggest that EM CD8(+) T cells in the SF are increased, likely because of inflammation, and they may be involved in modulating inflammation, thereby affecting the development and progression of RA.