Hirashima M, Fukazawa T, Abe K, Morita Y, Kusaoi M, Hashimoto H
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Lupus. 2004;13(1):24-31. doi: 10.1191/0961203304lu488oa.
The objective of this study was to determine the expression and activity of CTLA4 in T-cells of systemic lupus erythematosus (SLE) patients. Expression of CTLA4 on freshly isolated peripheral blood T-cells was evaluated in 33 SLE patients and 25 controls using flow cytometry. The T-cells from 19 SLE patients and 22 controls were stimulated and cultured with Chinese hamster ovary cells expressing CD80 (CHO-CD80) or with CHO cells. T-cell proliferation was determined with [3H] thymidine incorporation (CPM), and the inhibitory effect of CTLA4 on T-cell proliferation was evaluated by the ratio of CPM for T-cells with CHO-CD80 cells to that of T-cells with CHO cells (the CHO-CD80/CHO ratio). Intracellular CTLA4 expression in freshly isolated peripheral blood T-cells was significantly higher in SLE patients than the controls (P < 0.05), but there was no correlation with clinical features or disease activity. The CHO-CD80/CHO ratio of SLE patients was significantly higher than that of the controls (P < 0.05). Among SLE patients, the CHO-CD80/CHO ratio of patients with lupus nephritis was significantly higher than that of patients without lupus nephritis (P < 0.05). In conclusion, our data suggest that CTLA4 expression is not impaired in SLE patients, but there is a possibility of decreased inhibitory effect of CTLA4 involved in the pathogenesis of SLE.
本研究的目的是确定系统性红斑狼疮(SLE)患者T细胞中CTLA4的表达及活性。使用流式细胞术对33例SLE患者和25例对照者新鲜分离的外周血T细胞中CTLA4的表达进行评估。用表达CD80的中国仓鼠卵巢细胞(CHO-CD80)或CHO细胞刺激并培养19例SLE患者和22例对照者的T细胞。通过[3H]胸苷掺入法(CPM)测定T细胞增殖,并通过T细胞与CHO-CD80细胞的CPM与T细胞与CHO细胞的CPM之比(CHO-CD80/CHO比值)评估CTLA4对T细胞增殖的抑制作用。SLE患者新鲜分离的外周血T细胞中细胞内CTLA4表达显著高于对照者(P<0.05),但与临床特征或疾病活动度无相关性。SLE患者的CHO-CD80/CHO比值显著高于对照者(P<0.05)。在SLE患者中,狼疮性肾炎患者的CHO-CD80/CHO比值显著高于无狼疮性肾炎的患者(P<0.05)。总之,我们的数据表明SLE患者的CTLA-4表达未受损,但CTLA4的抑制作用可能降低,参与了SLE的发病机制。