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目的:研究系统性红斑狼疮(systemic lupus erythematosus,SLE)T细胞中CTLA-4的表达及临床意义。方法:分离正常人和SLE患者的外周血单个核细胞(peripheral blood mononuclear cells,PBMCs),以抗-CD3、抗-CD28刺激培养48 h,刺激培养前后收取细胞,以流式细胞术(FCM)检测CD4~+和CD8~+T细胞中CTLA-4~+细胞比例,并分析其与SLE疾病活动性指数(SLEDAI)和肾损害的关系。再以ELISA法检测培养上清中游离的CTLA-4水平。结果:SLE患者刺激前的CD4~+和CD8~+T细胞且主要是CD25~+T细胞中CTLA-4~+细胞的比例较正常人显著增高,与SLEDAI呈正相关;而其CD8~+CD28-T细胞中CTLA-4~+细胞比例也显著高于正常人,但与SLEDAI之间无显著相关性;经抗-CD3、抗-CD28抗体刺激后,其CD4~+CD25~+T细胞、CD8~+CD25~+T细胞或CD8~+CD28-T细胞中CTLA-4~+细胞的比例却显著低于正常人,但与SLEDAI之间无显著相关性,仅在活动性SLE患者中有肾损组的CD8~+CD28-T细胞中CTLA-4~+细胞的比例显著低于非肾损组;而且经刺激培养后SLE患者PBMC上清中游离的CTLA-4水平也显著低于正常人。结论:SLE患者新鲜分离的T细胞(CD4~+及CD8~+)中CTLA-4表达异常增高,反映T细胞异常活化和疾病活动;另一方面,SLE患者T细胞又存在CTLA-4诱导性表达障碍,可能与SLE T细胞体外再活化能力减弱有关。
Objective: To study the expression and clinical significance of CTLA-4 in systemic lupus erythematosus (SLE) T cells. Methods: Peripheral blood mononuclear cells (PBMCs) from normal and SLE patients were isolated and stimulated with anti-CD3 and anti-CD28 for 48 hours. Cells were harvested before and after culture. Flow cytometry (FCM) The proportion of CTLA-4 ~ + cells in CD4 ~ + and CD8 ~ + T cells was detected and their relationship with SLE disease activity index (SLEDAI) and renal damage were analyzed. The level of free CTLA-4 in the culture supernatant was detected by ELISA. Results: The proportion of CTLA-4 ~ + cells in pre-stimulation CD4 ~ + and CD8 ~ + T cells and predominantly CD25 ~ + T cells in SLE patients was significantly higher than that in normal subjects and positively correlated with SLEDAI; while CD8 ~ + CD28 The percentage of CTLA-4 ~ + cells in T-cells was also significantly higher than that in normal subjects, but not with SLEDAI. After stimulation with anti-CD3 and anti-CD28 antibodies, the percentage of CD4 ~ + CD25 ~ + T cells, The proportion of CTLA-4 ~ + cells in CD8 ~ + CD25 ~ + T cells or CD8 ~ + CD28-T cells was significantly lower than that in normal subjects but not in SLEDAI patients. Only in patients with active SLE The proportion of CTLA-4 ~ + cells in CD8 ~ + CD28-T cells in renal injury group was significantly lower than that in non-renal injury group; and the level of CTLA-4 in PBMC supernatant of SLE patients after stimulation was significantly lower than that in normal people. CONCLUSIONS: CTLA-4 expression in newly isolated T cells (CD4 ~ + and CD8 ~ +) in patients with SLE is abnormally increased, which reflects the abnormal activation and disease activity of T cells. On the other hand, CTLA-4 inducible The expression disorder may be related to the weakened reactivation ability of SLE T cells in vitro.