CD4+CD25high调节性T细胞在类风湿性关节炎病程中的消长及其意义

目的研究类风湿性关节炎(RA)患者病情发展不同阶段外周血及滑液中CD4 CD25high调节性T细胞数量的差别,及其与类风湿性关节炎活动程度的相关性,探讨CD4 CD25highT细胞在RA发生发展中所发挥的免疫抑制和调节作用。方法分别选取未经过缓解病情抗风湿药(DMARDs)治疗的活动性RA患者11例,经DMARDs治疗病情缓解的RA患者12例,和DMARDs治疗后效果不佳的RA患者9例,以及正常对照8例,检测他们的外周血淋巴细胞,以流式细胞术检测CD4 CD25high调节性T细胞的百分率,并研究CD4 CD25highT细胞百分率与抗环瓜氨酸(CCP)抗体,C反应蛋白(CRP),血沉(ESR)及类风湿因子(RF)的相关性。对其中部分患者的血液和关节滑液同时进行分析。结果RA未经治疗组和治疗效果不佳组CD4 CD25highT细胞的百分率(分别是5.24%和6.43%)明显低于正常对照组和治疗后病情缓解组(分别是17.17%和11.79%,P<0.01)。RA患者CD4 CD25highT细胞的百分率与抗CCP抗体(58.0Ru/mL),ESR(38.8mm/h)及CRP(2.73μg/L)呈明显负相关(P<0.05),与类风湿因子(RF=14.4Iu/mL)无明显的相关性(P=0.054)。正常对照组的CD4 CD25highT细胞百分率与抗CCP抗体(均<5.0Ru/mL),ESR(4.67mm/h),CRP(0.15μg/L)及RF(1.37)无明显相关性(P>0.1)。RA患者关节滑液中CD4 CD25highT百分率明显低于强直性脊柱炎(ankilosing spondylitis,AS)关节积液患者(P<0.05)。结论试验结果表明未经缓解病情治疗和治疗后效果不佳者的外周血中,CD4 CD25high调节性T细胞相对减少,且与病情活动程度负相关,这可能是RA发生和发展的一个重要因素。

The changes of CD4+CD25high regulatory T cells in the course of rheumatoid arthritis and their significances

AIM: To explore the percentages of CD4(+) CD25(high) regulatory T cells in peripheral blood or synovial fluid from patients with rheumatoid arthritis (RA) on different stages, and to study their correlations with the activity of the disease. METHODS: Peripheral blood lymphocytes were obtained from the patients with active RA who had received no previous disease modifying (DMARDs) therapy(n=11), from individuals with stable, well-controlled RA (n=12), from subjects whose disease were poorly improved after DMARDs therapy(n=9), and from healthy controls(n=8). The frequencies of CD4(+) CD25(high) T cells were quantified by using flow cytometry(FCM). Meanwhile, the correlations between the percentage of CD4(+) CD25(high) T cells and the level of Anti-CCP antibody, CRP, ESR and RF were also investigated. Paired blood and synovial fluid was analysed in a small group of RA and other patients. RESULTS: There was a smaller proportion of CD4(+) CD25(high) T cells in the peripheral blood of the active RA patients(mean 5.24%) and poorly-improved RA patients(mean 6.43%) than in patients with stable well-controlled RA or in healthy controls(mean 11.79% and 17.17%, respectively, P<0.01 in each case). The frequency of CD4(+) CD25(high) T cells from RA was negatively associated with Anti-CCP antibody(58.0 Ru/mL), ESR(38.8 mm/h) and CRP(2.73 mug/L), (P<0.05 for each). On contrast, The frequency of CD4(+) CD25(high) T cells from healthy controls was not significantly correlated with the level of Anti-CCP antibody(<5.0 Ru/mL), ESR(4.67 mm/h), CRP(0.15 mug/L) and RF(1.37) (all P>0.1). The percentage of CD4(+) CD25(high) regulatory T cells from synovial fluid of RA patients (24.32%) was significantly lower than that of AS patients(30.24%) (P<0.05). CONCLUSION: The results demonstrate a smaller CD4(+) CD25(high) regulatory T cell population in peripheral blood of individuals with active RA prior to disease modifying treatment and with poorly-improved RA, and this is negatively associated with the activity of the disease.