类风关滑膜浸润T细胞特性与致病机制研究

为研究类风湿关节炎时关节滑膜浸润性T细胞生物学特性与致病机制 ,对 10例RA患者滑膜液中淋巴细胞的免疫表型、细胞因子分泌格局与趋化因子受体表达进行了分析。用双色荧光标记法分别测定滑膜液中和外周血淋巴细胞表型与趋化因子受体表达。用ELISA方法检测滑膜液与外周血中IFN γ、IL 10、IL 4与IL 12的含量。结果是滑膜液中的CD4 + T淋巴细胞为 4 0 0 %± 11% ,CD8+ T细胞为 34 0 %± 6 % ,CD4 + 与CD8+ T细胞的比值为 1 2 ,显著低于外周血中CD4 /CD8的比值。滑膜液中CD3和CD2 5双阳性的活化T细胞占 16 %± 6 0 %。趋化因子受体CCR5表达较低 ,与外周血无明显差异。但CX CR3表达水平较高 ,为 16 %± 4 0 % ,远远高于外周血 (仅为 0 5 %± 0 3% )。IFN γ在滑膜液中含量很高 ,达 (36 6 7± 4 3 2 )pg/ml,而外周血中含量仅为 (2 0 1± 3 2 )pg/ml。IL 4含量未能测得 (<15pg/ml ) ,与外周血相似。IL 12含量为 (4 19 9±89 2 )pg/ml,远高于外周血中的含量 (6 5 32± 34 2 )pg/ml。IL 10含量为 (187 7± 34 5 )pg/ml,高于外周血中的含量 (85±12 7)pg/ml。在所测细胞因子中 ,关节滑膜液中IFN γ和IL 12的含量与外周血相比具有显著的统计学差异。表明RA关节滑膜液中有相当数量的T细胞浸润。这些T细胞

Study on the Characteristics and Pathogenesis of the Infiltrating T Cells in Synovial Fluid of Patients with Rheumatoid Arthritis

To study the characteristics and pathogenesis of infiltrating T cells in synovial fluid of patients with rheumatoid arthritis,the phenotype,pattern of cytokine secretion and expression of chemokine receptors of lymphocytes in synovial fluids of 10 patients were investigated by immunofluorscence using flow cytometry analysis.It was found that the percentages of CD4 + and CD8 +T cells infiltrating in the synovial fluids were 40.0%±11% and 34.0%±6% respectively,and CD4/CD8 ratio was 1.2,which was much lower than that in the peripheral blood mononuclear cells (PBMC). The percentage of CD3/CD25 double positive T cells was 16.0%±6%,and the expression of chemokine receptor CCR5 on the synovial fluid monocytes was rather low,without significant difference between that expressed on PBMC. But the expression of another chemokine receptor CXCR3 on the synovial fluid monocytes (16.0%±4%) was higher than that on PBMC (0.5%±0.3%). The level of IFN-γ in the synovial fluid was (366.7±43.2) pg/ml,which was much higher than that in serum (20.1%±3.2) pg/ml,and the level of IL-4 was very low and hard to be detected (<15 pg/ml) in both of synovial fluid and serum. The amounts of other cytokines,IL-12 and IL-10 in synovial fluid were 419.9±89.2 pg/ml and (187.7±34.5) pg/ml respectively.In contrast to those in sunovial fluid,the levels of IL-2 and IL-10 in sera were (65.32±34.2) pg/ml and (85.0±12.7) pg/ml respectively. Experimental results suggest that there are considerable amount of T lymphocyte infiltration in the synovial fluids of patients with rheumatoid arthritis with high expressions of CD25 and CCR5. The levels of IFN-γ and IL-12 were much higher than that in sera,indicating a Th1 type of cytokine profile in synovial fluids,and a high expressions of CXCR3 on synovial fluid monocytes suggesting that this molecule could enhance the infiltration on synovial membrane produced by inflammatory cells,so that involved in the lesions of joint tissues in patients with rheumatoid arthritis.