T细胞亚群与细胞因子在矽肺患者外周血中的表达及其意义

Expression of T cell subgroup and cytokines in the peripheral blood of patients with silicosis and their significance

目的 探讨矽肺患者外周血中T细胞亚群（CD3＋、CD4＋、CD8＋、CD4＋CD25 high 调节性T细胞）的表达和血清细胞因子的水平及其意义.方法 选取苏州市第五人民医院住院矽肺患者106例为研究对象,56例健康体检者为正常对照.采用流式细胞术测定患者和对照者外周血CD3＋、CD4＋、CD8＋和CD4＋CD25 high 调节性T细胞（Treg）;采用酶联免疫化学发光法测定外周血血清中可溶性白介素2受体（sIL-2R）、白介素6（IL-6）,白介素8（IL-8）及肿瘤坏死因子α（TNF-α）.结果 （1）矽肺组患者外周血CD3＋、CD4＋、CD8＋百分比均低于正常对照组（t值分别为3.755、3.828、2.347,P均〈0.05）,Treg细胞百分比高于正常对照组,差异有统计学意义（t=-8.345,P〈0.05）,各分期组和对照组间比较,经单因素方差分析,CD3＋、CD4＋、CD4＋CD25 high细胞差异均有统计学意义（F值分别为5.620、8.007、26.71,P均〈0.05）,其中CD4＋ T细胞在Ⅲ期矽肺组中低于Ⅰ期矽肺组,差异有统计学意义（t=3.424,P〈0.05）;各分期组Treg细胞百分比与正常对照组比较差异亦均有统计学意义（t值分别为-7.934、-9.445、-5.096,P均〈0.05）.（2）矽肺组患者外周血sIL-2R、IL-6、IL-8与TNF-α水平均高于正常对照组,差异均有统计学意义（t值分别为-6.952、-4.506、-2.551、-5.670,P均〈0.05）;各分期组和对照组间比较,经单因素方差分析,sIL-2R、IL-6与TNF-α差异均有统计学意义（F值分别为11.03、11.31、13.22,P均〈0.0001）,其中Ⅲ期患者sIL-2R高于Ⅰ期患者（t=-2.882）,Ⅱ期、Ⅲ期患者IL-6明显高于Ⅰ期患者（t值分别为-3.022、-2.632）,Ⅱ期患者TNF-α高于Ⅰ期患者（t=-2.322）,差异均有统计学意义（P均〈0.05）.（3）矽肺组患者外周血Treg细胞水平与CD3＋、CD8＋百分比均呈负相关（r值分别为-0.357、-0.508,P均〈0.05）;sIL-2R分别与IL-6、IL-8、TNF-α呈正相关（r值分别为0.483、0.199、0.392,P均〈0.05）;TNF-α分别与IL-6、IL-8呈正相关（r值分别为0.338、0.338,P均〈0.05）.结论 矽肺患者外周血T细胞亚群表达异常,Treg细胞水平明显增高,细胞因子调节免疫功能紊乱,可能与矽肺发病机制有关,这些指标的检测对疾病的诊断、分期、病情监测和预后判断有一定意义.

Objective To explore the expression of peripheral T cell subgroup （CD3＋,CD4＋,CD8＋,CD4＋CD25 high regulatory T cells） and the level and significance of serum cytokines in patients with silicosis.Methods One hundred and six cases patients with silicosis were collected in the Fifth People＇＇s Hospital of Suzhou as study subjects and 56 healthy subjects as control group.Flow cytometry was used to detect the peripheral CD3＋,CD4＋,CD8＋ and CD4＋CD25 high regulatory T cells （Treg） of the patients and the control group,while chemiluminescence immunoassay was utilized to measure the peripheral serum soluble interleukin-2 receptor （sIL-2R）,interleukin 6 （IL-6）,interleukin 8 （IL-8） and tumor necrosis factor α （TNF-α）.Results （1） The percentages of peripheral CD3＋,CD4＋ and CD8＋ in the silicosis group were all lower than those in the control group （t=3.755,3.828,2.347,P〈0.05）;the percentage of Treg cells was higher in the silicosis group than in the control group,the difference was statistically significant （t=-8.345,P〈0.05）.Compared with the control group,based on the one-way analysis of variance,the differences in CD3＋,CD4＋,CD8＋ and CD4＋CD25 high cells were all statistically significant （F=5.620,8.007,26.71,P〈0.05）;in the silicosis group,the percentage of CD4＋ T cells was lower in stage III than in stage I （t=3.424,P〈0.05）;compared with the control group,the percentages of Treg cells in the silicosis group were lower in all stages （t=-7.934,-9.445,-5.096,P〈0.05）.（2） The levels of peripheral sIL-2R,IL-6,IL-8 and TNF-α in the silicosis group were higher than those in the control group,the difference were statistically significant（t=-6.952,-4.506,-2.551,-5.670,P〈0.05）;compared with the control group,based on the one-way analysis of variance,the differences in sIL-2R,IL-6 and TNF-α in all stages were statistically significant （F=11.03,11.31,13.22,P〈0.0001）;the sIL-2R was higher in patients with stage III silicosis than that of stage I （t=-2.882,P〈0.05）;IL-6 was significantly higher in stage II and III silicosis group than that of stage I group （t=-3.022,-2.632,P〈0.05）,and TNF-α was higher in patients with stage II silicosis than patients with stage I silicosis （t=-2.322,P〈0.05）.（3） The level of peripheral Treg cells was negatively correlated with the percentages of CD3＋ and CD8＋ cells in patients with silicosis （r=-0.357,-0.508,P〈0.05）;sIL-R2 was positively correlated with IL-6,IL-8 and TNF-α,respectively （r=0.483,0.199,0.392,P〈0.05）;TNF-α was positively correlated with IL-6 and IL-8,respectively （r=0.338,0.338,P〈0.05）.Conclusion Patients with silicosis have abnormal expression in peripheral T cell subgroups,significantly increased Treg cell and dysfunctional cytokines,which may be associated with the pathogenesis of silicosis,the detection of these indicators may have significance of diagnosis,staging,disease monitoring and prognosis of the diseases.