Chemokine Receptor CCR4 on CD4+ T Cells in Juvenile Rheumatoid Arthritis Synovial Fluid Defines a Subset of Cells with Increased IL-4:IFN-γ mRNA Ratios1-猫眼课题宝

幼年类风湿关节炎滑液中 CD4+ T 细胞上的趋化因子受体 CCR4 定义了 IL-4:IFN-γ mRNA 比率增加的细胞亚群1

DOI：

发表时间：

2001

期刊：

Journal of Immunology

影响因子：

4.4

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

S. Thompson;L. Luyrink;T. Graham;M. Tsoras;Mary Ryan;M. Passo;D. Glass

为了了解促进儿童炎症关节内T细胞募集和存活的机制，我们使用三色流式细胞术分析研究了幼年型类风湿关节炎（JRA）患者滑液T细胞和匹配外周血样本中CCR 4和CCR 5的表达。通过ELISA测定JRA滑液、JRA血浆、成人类风湿性关节炎滑液和正常血浆中的趋化因子和活化调节的趋化因子以及巨噬细胞衍生的趋化因子（CCR 4配体）。在CD 4 +/CCR 4+和CD 4 +/CCR 4 −细胞亚群中评估IL-4和IFN-γ mRNA的产生。我们发现JRA滑液中CCR 4+和CCR 5 + T细胞的积累以及疾病过程早期收集的样本中CCR 4 + T细胞数量增加的相关性。在JRA滑液和血浆样本中检测到Thr和活化调节的趋化因子，但在成人类风湿关节炎滑液或对照血浆中未检测到Thr和活化调节的趋化因子。巨噬细胞衍生的趋化因子存在于所有样品中。与CD 4 +/CCR 4 −细胞相比，CD 4 +/CCR 4+滑膜淋巴细胞产生更多的IL-4和更少的IFN-γ。这些发现表明，JRA关节中的CCR 4 + T细胞可能在疾病早期通过产生2型细胞因子发挥抗炎作用，并可能在确定疾病表型中发挥作用。

To understand the mechanisms that promote recruitment and survival of T cells within the pediatric inflamed joint, we have studied the expression of CCR4 and CCR5 on synovial fluid T cells and matched peripheral blood samples from juvenile rheumatoid arthritis (JRA) patients using three-color flow cytometric analysis. Thymus- and activation-regulated chemokine and macrophage-derived chemokine, ligands for CCR4, were measured by ELISA in JRA synovial fluid, JRA plasma, adult rheumatoid arthritis synovial fluid, and normal plasma. IL-4 and IFN-γ mRNA production was assessed in CD4+/CCR4+ and CD4+/CCR4− cell subsets. We found accumulations of both CCR4+ and CCR5+ T cells in JRA synovial fluids and a correlation for increased numbers of CCR4+ T cells in samples collected early in the disease process. Thymus- and activation-regulated chemokine was detected in JRA synovial fluid and plasma samples, but not in adult rheumatoid arthritis synovial fluid or control plasma. Macrophage-derived chemokine was present in all samples. CD4+/CCR4+ synovial lymphocytes produced more IL-4 and less IFN-γ than CD4+/CCR4− cells. These findings suggest that CCR4+ T cells in the JRA joint may function early in disease in an anti-inflammatory capacity through the production of type 2 cytokines and may play a role in determining disease phenotype.