Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis
Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis
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DOI：
10.1002/art.10622
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发表时间：
2002-11-01
影响因子：
--
通讯作者：
Miyasaka, N
中科院分区：
文献类型：
--
作者：
Nanki, T;Imai, T;Miyasaka, N
目标。类风湿性关节炎（RA）以多个关节的慢性炎症为特征。大量产生1型细胞因子的T细胞渗入RA滑膜。趋化因子和趋化因子受体被认为与T细胞浸润有关。在本研究中，我们研究了CX3CL1/fractalkine及其受体CX3C趋化因子受体1 （CX3CR1）在T细胞向RA滑膜迁移中的作用。利用流式细胞术、免疫组织化学和逆转录聚合酶链反应，我们分析了RA患者外周血和滑膜T细胞中CX3CR1的表达，以及滑膜中CX3CL1的表达。流式细胞术检测cx3cr1阳性T细胞细胞因子和细胞毒分子的表达。CX3CR1在RA患者外周血CD4+和CD8+ T细胞中的表达上调。外周表达CX3CR1的CD4+和CD8+ T细胞主要产生干扰素γ和肿瘤坏死因子α，并表达颗粒酶A和穿孔素等细胞毒性分子。CX3CR1+、CD3+ T细胞向RA滑膜浸润。CX3CL1是CX3CR1的唯一配体，在RA滑膜内皮细胞和滑膜细胞中表达，而在骨关节炎滑膜中不表达。我们的研究结果表明，CX3CL1和CX3CR1的相互作用可能有助于在RA滑膜中表达1型细胞因子并具有细胞毒性颗粒的CX3CR1+ T细胞的积累。
Objective. Rheumatoid arthritis (RA) is characterized by chronic inflammation of multiple joints. Large numbers of T cells, which produce type 1 cytokines, infiltrate into RA synovium. Chemokines and chemokine receptors are considered to contribute to the T cell infiltration. In this study, we examined the role of CX3CL1/fractalkine and its receptor CX3C chemokine receptor 1 (CX3CR1) in the T cell migration into RA synovium.Methods. Using flow cytometry, immunohistochemistry, and reverse transcription-polymerase chain reaction, we analyzed CX3CR1 expression by peripheral blood and synovial T cells, and CX3CL1 expression in synovium from patients with RA. Cytokine and cytotoxic molecule expression by CX3CR1-positive T cells was analyzed by flow cytometry.Results. CX3CR1 expression by peripheral CD4+ and CD8+ T cells was up-regulated in RA patients. The peripheral CD4+ and CD8+ T cells expressing CX3CR1 predominantly produced interferon-gamma and tumor necrosis factor alpha, and expressed cytotoxic molecules such as granzyme A and perforin. Furthermore, CX3CR1+,CD3+ T cells infiltrated into RA synovium. CX3CL1, the unique ligand of CX3CR1, was expressed by endothelial cells and synoviocytes in RA synovium, but not in osteoarthritis synovium.Conclusion. Our findings suggest that the interactions of CX3CL1 and CX3CR1 might contribute to the accumulation of CX3CR1+ T cells expressing type 1 cytokines and possessing cytotoxic granules in RA synovium.