来氟米特对狼疮肾炎患者T细胞表面共刺激分子谱影响的体外研究  

Effect of leflunomi de on the superficial costimulatory molecules spectrum of peripheral blood T lymphocytes in patients with lupus nephritis

作　　者：董光富[1] 李玲[1] 张晓[1] 雷云霞[1] 张光锋[1] 

机构地区：[1]广东省医学科学院广东省人民医院风湿免疫科,510080

出　　处：《中华风湿病学杂志》2010年第12期811-814,共4页Chinese Journal of Rheumatology

基　　金：广东省自然科学基金（04300905）

摘　　要：目的了解来氟米特（LEF）对狼疮肾炎（LN）患者外周血T淋巴细胞表面共刺激分子谱的表达模式有无作用。方法密度梯度离心法提取LN患者及健康对照外周血单个核细胞（PBMCs），设立4个培养组：空白组，植物血凝素（PHA）组，LEF组，PHA＋LEF组。双色标记流式细胞术检测PBMCs中T细胞表面分子CD28，CD40L，淋巴细胞功能相关抗原（EVA）-1a和细胞毒T淋巴细胞相关抗原（CTLA）-4的表达水平。多组间比较采用单因素方差分析。结果活动性LN组外周血T细胞表面CD28、CD40L、LFA-1a．和CTLA-4表达水平较健康对照组明显上调CD28：33．4±6．5和14．4±3．2；CD40L：13．2±3．2和5．4±2-3：LFA-1a：8．5±2.3和2．2±1．1；CTLA-4：4．6±1．5（P均〈0．01）；PHA可诱导健康对照T细胞表面CD28和CD40L表达明显上调CD28：26．8＋6．7和14．4＋3．2；CD40L：13．9±4．9和5．4±2．3（P均〈0．01），但对其CTLA-4和LFA-1α的表达无明显影响（P均〉0．05）；而PHA对活动性LN组外周血T细胞表面上述指标表达均有明显上调作用CD28：54．8±9．5和33．4±6．5；CD40L：49．9±9．1和13．3±3．2；LFA—1a：25．5±7．5和8．5±2．3；CTLA-4：10．5±2．8和7．7±1．4（P均〈0．05）；LEF活性代谢产物A771726对健康人外周血T细胞表面上述指标的表达无明显影响，但可逆转活动性LN患者外周血T细胞表面的CD40L、LFA-1α过度表达（P均〈0．05），对其CD28和CTLA-4过度表达无明显影响（P均〉0．05）；且A771726对PHA所诱导的活动性LN患者外周血T细胞表面CD28、CD40L和LFA—1a表达增加亦有明显抑制（P均〈0．05）。结论LEF可下调活动性LN患者外周血T细胞CD40L和LFA—1a表达，而对其CD28和CTLA-4表达无明显抑制作用，可能是其有效治疗LN的重要机制之一.Objective To investigate the effect of leflunomide on the superficial costimulatory molecules expression of T lymphocytes in patients with lupus nephritis （LN）. Methods The peripheral blood mononuclear cells （PBMCs） of female active LN patients and healthy female were separated by density grad- ient centrifugation, and cultured by phytohemagglutinin （PHA） or leflunomide active metabolites（A771726）. The CD28, CD40L, CTLA-4 and LFA-Ia expressions on the peripheral blood T lymphocytes were detected by double-colored now cytometry. The differences of the means were tested by analysis of variance（ANOVA） and SNK q test. Results Comparing with healthy controls, there were significantly higher expressions of CD28, CD40L, LFA-1a and CTLA-4 on the peripheral blood T cells in active LN patients （CD28：33.4±6.5 vs14.4± 3.2; CD40L： 13.2＋3.2 vs 5.4±2.3; LFA-la： 8.5±2.3 vs2.2±1.1; CTLA-4：4.6±1.5 all P〈0.01） as welt as CD28 and CD40L expression on the peripheral blood T cells from healthy controls induced by PHA （CD28： 26.8±6.7 vs14.4±3.2; CD40L： 13.9±4.9 us 5.4±2.3 all P〈0.01 ）, but not CTLA-4 and LFA-1a expression. However, CD28, CD40L, LFA-1a and CTLA-4 expressions on T ceils stimulated by PHA increased in active LN patients（all P〈0.05）. A771726 could significantly inhibit over-expression of LFA-la and CD40L on the T cells from active LN patients （CD40L：8.2±2.0 vs13.3±3.2;LFA-la：5.1±1.3 vs8.5±2.3 all P〈0,01）, but not CD28 and CTLA-4 expression. A771726 did not inhibit CD28, CD40L, LFA-1a and CTLA-4 expression on the T cells in healthy controls. Furthermore, A771726 could markedly inhibit the over-expression of all of the above molecules induced by PHA on the T cells of active LN patients （all P〈0.05）. Conclusion One of the major mechanisms for LEF treatment of LN is that LEF can down-regulate CD40L and LFA-la expression but not CD28 and CTLA-4 expression on the peripheral blood T cells in active LN patients.

关 键 词：狼疮肾炎 T淋巴细胞 表面共刺激分子谱 来氟米特 

分 类 号：R686[医药卫生—骨科学]