Evidence of the Transient Nature of the Th17 Phenotype of CD4+CD161+T Cells in the Synovial Fluid of Patients With Juvenile Idiopathic Arthritis
Evidence of the Transient Nature of the Th17 Phenotype of CD4+CD161+T Cells in the Synovial Fluid of Patients With Juvenile Idiopathic Arthritis
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DOI：
10.1002/art.30332
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发表时间：
2011-08-01
影响因子：
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通讯作者：
Annunziato, Francesco
中科院分区：
文献类型：
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作者：
Cosmi, Lorenzo;Cimaz, Rolando;Annunziato, Francesco
Objective.研究少关节型幼年特发性关节炎（JIA）患儿关节滑液（SF）中CD 4 + T细胞的表型和功能，并探讨其与疾病活动性的可能联系。从23例少关节型JIA患儿和15例健康儿童外周血中提取CD 4 + T细胞。分析细胞的CXCR 3、CCR 6和CD 161的表达以及干扰素-γ和白细胞介素-17A（IL-17 A）的产生。进行谱分析和克隆型分析以评估不同的T细胞亚群。JIA患儿SF中Th 1或Th 17/Th 1表型的CD 4 + CD 161+细胞数高于PB。JIA SF的少数Th 17细胞在体外自发转变为Th 1表型，而健康儿童PB的Th 17细胞仅在JIA SF存在下发生转变;这种效应被IL-12活性的抗体阻断所中和。谱分析和克隆型分析显示，同一JIA患者SF中的CD 161 + Th 17细胞和CD 161 + Th 1细胞中T细胞受体V（β）库存在类似的倾斜。JIA SF中CD 4 + CD 161+细胞，尤其是Th 17/Th 1细胞与血沉、C反应蛋白水平呈正相关。这些发现表明，CD 4 + CD 161 + T细胞从Th 17向Th 17/Th 1或Th 1表型的转变可以发生在少关节型JIA儿童的SF中，并表明这些细胞的积累与炎症参数相关。因此，这些结果支持了这一假设，即这些细胞可能在JIA疾病活动中发挥作用。
Objective. To investigate the phenotype and function of CD4+ T cells in synovial fluid (SF) from the affected joints of children with oligoarticular-onset juvenile idiopathic arthritis (JIA), and to establish a possible link with disease activity.Methods. CD4+ T cells were obtained from the peripheral blood (PB) and SF of 23 children with oligoarticular-onset JIA, as well as from the PB of 15 healthy children. The cells were analyzed for the expression of CXCR3, CCR6, and CD161 and for the production of interferon-gamma and interleukin-17A (IL-17A). Spectratyping and clonotype analyses were performed to assess different T cell subsets.Results. The numbers of CD4+CD161+ cells showing either the Th1 or the Th17/Th1 phenotype were higher in the SF than in the PB of children with JIA. The few Th17 cells from JIA SF underwent a spontaneous shift to the Th1 phenotype in vitro, whereas Th17 cells from the PB of healthy children shifted only in the presence of JIA SF; this effect was neutralized by antibody blockade of IL-12 activity. Spectratyping and clonotype analyses showed a similar skewing of the T cell receptor V(beta) repertoire in both CD161+ Th17 cells and CD161+ Th1 cells derived from the SF of the same JIA patient. The frequencies of CD4+CD161+ cells, particularly the Th17/Th1 cells, in the JIA SF positively correlated with the erythrocyte sedimentation rate and levels of C-reactive protein.Conclusion. These findings suggest that a shifting of CD4+CD161+ T cells from Th17 to the Th17/Th1 or Th1 phenotype can occur in the SF of children with oligoarticular-onset JIA, and indicate that the accumulation of these cells is correlated with parameters of inflammation. Thus, the results support the hypothesis that these cells may play a role in JIA disease activity.