类风湿关节炎患者外周血TCRαβ+CD4-CD8-T细胞与FAS介导的凋亡关系研究

Relationship between peripheral TCRαβ+CD4-CD8-T cells and FAS-mediated apoptosis in patients with rheumatoid arthritis

摘要:

目的：检测类风湿关节炎（Rheumatoid arthritis,RA）患者外周血中TCRαβ+细胞、CD4-CD8- 细胞、TCRαβ+CD4-CD8-T细胞(Double negative T cells,DNT细胞)及各细胞亚群表面凋亡相关蛋白FAS的表达情况，探讨RA患者TCRαβ+CD4-CD8-T细胞与FAS介导的凋亡之间的关系。方法:选取24例RA患者以及24例同期健康查体者作为研究对象，检测所有研究对象外周血TCRαβ+细胞、CD4-CD8- 细胞、TCRαβ+CD4-CD8-细胞、TCRαβ+细胞、CD4-CD8-细胞、TCRαβ+CD4-CD8-T细胞的数量及表面凋亡相关蛋白FAS的表达情况，并分析以上指标与类风湿因子（Rheumatoid factors,RF）、白细胞数（White blood cell,WBC）、急性时相反应蛋白（C-reactive protein,CRP）以及血沉(Erythrocyte sedimentation rate,ESR)之间的相关性。结果：RA患者外周血TCRαβ+细胞、CD4-CD8-细胞与健康对照相似，TCRαβ+CD4-CD8-T细胞数量显著高于健康对照(0.82±0.38 vs.0.57±0.26,P=0.013)，TCRαβ+CD4-CD8-T细胞表面的FAS的表达增高(1.23±0.69 vs.0.80±0.45,P=0.016)，并与TCRαβ+CD4-CD8-T细胞数量呈显著正相关关系（r=0.809,P=0.000）；TCRαβ+细胞及其表面表达的FAS受体、CD4-CD8-细胞及其表面表达的FAS受体、TCRαβ+CD4-CD8-T细胞及其表面表达的FAS受体与RF、WBC、CRP以及ESR之间均无相性(P>0.05)。结论：RA患者外周血中TCRαβ+CD4-CD8-T细胞及其表面表达的FAS受体显著增加，表明TCRαβ+CD4-CD8-T细胞对FAS介导的凋亡敏感性增加，可能会导致免疫反应性T细胞的比例失调。RA患者中TCRαβ+CD4-CD8-T细胞及其表面表达的FAS受体与疾病活动性指标之间无相关关系，TCRαβ+CD4-CD8-T细胞及其表面表达的FAS受体在RA患者的发病机制中的作用还有待于进一步探讨。

Abstract:

Objective:To investigate the expression of FAS receptor on idiosyncratic T cell subsets,including TCRαβ+cells,CD4-CD8-cells and TCRαβ+CD4-CD8-T cells,and to discuss the relationship between FAS-mediated apoptosis and peripheral TCRαβ+CD4-CD8-T cells in patients with rheumatoid arthritis(RA).Methods:Totally 24 RA patients and 24 normal controls were included.Flow cytometry was used to detect the percentages of T cell subsets and the expression of FAS receptor.The relationships between the percentages of T cell subsets and the expression of FAS receptor with RF,WBC,CRP and ESR were analyzed respectively by spearman relativity analysis.Results:The percentages of peripheral TCRαβ+ cells and CD4-CD8-cells from RA patients were similar to those in normal controls (P>0.05).Strikingly higher levels of TCRαβ+CD4-CD8-T cells in the peripheral blood of RA patients were detected compared with those in normal controls (0.82±0.38 vs.0.57±0.26, P=0.013).The expressions of FAS receptor on TCRαβ+CD4-CD8-T cells were significantly increased in RA patients compared with those in normal controls (1.23±0.69 vs.0.80±0.45,P=0.016).Positively relationship was found between TCRαβ+CD4-CD8-T cells and TCRαβ+CD4-CD8-FAS+ cells(r=0.809,P=0.000).There was no significant relationship between the percentages of TCRαβ+CD4-CD8-Tcells,the level of FAS receptor expression and RF,WBC,CRP or ESR,respectively.TCRαβ+ cells as well as CD4-CD8- cells had no significant association with RF,WBC,CRP and ESR,respectively.Conclusion: The preliminary results suggest that the significantly upregulated percentages of DNT cells and its FAS receptor expression may increase the sensitivity to FAS-mediated apoptosis.It may lead to the imbalance of immune respective T cells in RA patients.There is no significant relationship between the percentages of TCRαβ+CD4-CD8-T cells,FAS receptor and the indicators of disease activity,though the percentages of them are markedly increased in the Chinese RA patients.The role of TCRαβ+CD4-CD8-T cells in the pathogenesy of RA patients remains to be further studied.