Blaschke Sabine, Middel Peter, Dorner Brigitte G, Blaschke Volker, Hummel Klaus M, Kroczek Richard A, Reich Kristian, Benoehr Peter, Koziolek Michael, Müller Gerhard A
Department of Nephrology and Rheumatology, Georg-August-University, Robert-Koch Strasse 40, Göttingen 37075, Germany.
Arthritis Rheum. 2003 Jul;48(7):1858-72. doi: 10.1002/art.11171.
To evaluate the possible role of activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin (Lptn) in the pathogenesis of rheumatoid arthritis (RA).
ATAC/Lptn levels in serum and synovial fluid samples were measured by sandwich enzyme-linked immunosorbent assay. Expression of messenger RNA for ATAC/Lptn in synovial tissues was analyzed by reverse transcription-polymerase chain reaction (PCR) and by in situ hybridization, and was quantitated by real-time PCR. The phenotype of peripheral blood mononuclear cells (PBMCs) expressing ATAC/Lptn was analyzed by intracellular cytokine staining and flow cytometry.
Levels of ATAC/Lptn were similar in sera and synovial fluids from RA patients (n = 20) and osteoarthritis controls (n = 15). In phorbol myristate acetate/ionomycin-stimulated PBMCs, ATAC/Lptn expression was detected in CD8+ T cells and in a significantly increased proportion of CD4+,CD28- T cells from RA patients as compared with healthy controls. In synovial tissues, ATAC/Lptn was predominantly localized in CD3+ T cells in the sublining layer. Lymphocytes, synovial macrophages, and, unexpectedly, fibroblast-like synoviocytes (FLS) were identified as major target cells for ATAC/Lptn in RA synovium, as determined by analysis of the ATAC/Lptn receptor XCR1. In vitro, ATAC/Lptn stimulation of FLS resulted in a marked down-regulation of matrix metalloproteinase 2 production.
These data indicate that in RA synovium, ATAC/Lptn is mainly produced by T cells. Considering its function as a lymphocyte-specific chemoattractant, ATAC/Lptn might be a key modulator for T cell trafficking in the pathogenesis of RA. In addition, functional studies suggest that ATAC/Lptn may exert additional immunomodulatory effects in RA.
评估活化诱导的、T细胞衍生的趋化因子相关细胞因子（ATAC）/淋巴细胞趋化因子（Lptn）在类风湿关节炎（RA）发病机制中的可能作用。
采用夹心酶联免疫吸附测定法检测血清和滑液样本中ATAC/Lptn水平。通过逆转录-聚合酶链反应（PCR）、原位杂交分析滑膜组织中ATAC/Lptn信使核糖核酸的表达，并通过实时PCR进行定量分析。采用细胞内细胞因子染色和流式细胞术分析表达ATAC/Lptn的外周血单个核细胞（PBMC）的表型。
类风湿关节炎患者（n = 20）和骨关节炎对照者（n = 15）的血清和滑液中ATAC/Lptn水平相似。在佛波酯/离子霉素刺激的PBMC中，与健康对照相比，类风湿关节炎患者的CD8⁺ T细胞以及CD4⁺、CD28⁻ T细胞比例显著增加的细胞中可检测到ATAC/Lptn表达。在滑膜组织中，ATAC/Lptn主要定位于衬里层的CD3⁺ T细胞中。通过对ATAC/Lptn受体XCR1的分析确定，淋巴细胞、滑膜巨噬细胞以及出人意料的成纤维样滑膜细胞（FLS）是类风湿关节炎滑膜中ATAC/Lptn的主要靶细胞。在体外，ATAC/Lptn刺激FLS导致基质金属蛋白酶2产生显著下调。
这些数据表明，在类风湿关节炎滑膜中，ATAC/Lptn主要由T细胞产生。考虑到其作为淋巴细胞特异性趋化因子的功能，ATAC/Lptn可能是类风湿关节炎发病机制中T细胞迁移的关键调节因子。此外，功能研究表明，ATAC/Lptn可能在类风湿关节炎中发挥额外的免疫调节作用。
