共刺激分子CD28 CD152在类风湿关节炎患者T细胞亚群上表达异常的研究

目的观察共刺激分子CD28,CD152在类风湿关节炎(RA)患者的T细胞亚群上的表达异常情况,探讨RA的发病机制及治疗手段.方法用流式细胞仪采用直接免疫荧光法测定39例RA患者和20名健康对照人外周血T细胞表面标志CD3,CD4,CD8的表达情况及CD28,CD152在CD4+T和CD8+T细胞上的表达.结果 RA患者CD3+CD4+细胞较正常对照组显著增高(P＜0.01),CD3+CD8+细胞较正常对照组显著降低(P＜0.05),CD4+T细胞上CD28的表达较对照组显著降低(P＜0.05),而CD8+T细胞上CD28的表达与对照组差异无显著性(P＞0.05);CD4+T和CD8+T细胞上CD152的表达都较对照组显著增高(P＜0.01).结论在RA患者的细胞免疫活化过程中首先表现为B7/CD28信号途径占优势,T细胞被激活,激活的T细胞大量分泌CD152,它与CD28竞争结合B7分子,CD152/B7途径转而占优势,下调或终止T细胞反应.同时CD28+细胞数目的减少或功能缺陷造成RA患者外周血单个核细胞凋亡加速,是诱发RA患者的局部病理损害的原因.阻断CD152和B7的相互作用可增强特异性T细胞应答,为RA的免疫学治疗提供理论依据.

Study of CD28,CD152 costimulatory molecules expression on subpopulation of T cells in rheumatoid arthritis patients

Objective To investigate the relationship between abnormal expression of CD28, CD152 costimulatory molecules on subpopulation of T cells and the immune dysfunction in patients with rheumatoid arthritis (RA). Methods CD3, CD4, CD8, CD28, CD152 on the surface of T cells were labeled by immuno-fluorescence and determined by flow cytometry. Results As compared with control, CD3+CD4+ T cells were significantly higher (P<0.01), while CD3+CD8+ T cells were significantly lower (P<0.05). CD28 on CD4+Tcells was significantly lower (P<0.05), while CD28 on CD8+T cells was neither higher nor lower(P>0.05).CD152 on CD4+T and CD8+T cells were both significantly higher (P<0.01). Conclusion In RA patients the initial reaction of cellular immunity is B7/CD28 pathway activation. It activates T cells, then a great deal of CD152 is secreted. It combines with B7 and inhibits T cells. The decrease of CD28 causes AICD of lymphocytes in RA patients, then induces pathological injuries. Blocking of CD152/B7 pathway is helpful in RA treatment.