霉酚酸衍生物对小鼠T细胞免疫功能的抑制作用

目的研究2种新型霉酚酸衍生物(代号JU95-07B、JU100-07E)在体外对小鼠T细胞免疫功能的影响。方法小鼠脾细胞用抗CD3单克隆抗体(mAb)刺激,同时加入不同浓度(10-4、10-5、10-6、10-7、10-8mol/L)及在不同时间点(刺激细胞后第0、6、12 h)加入同一浓度(10-5mol/L)的霉酚酸衍生物后,用酶联免疫吸附法(ELISA)检测培养上清中IFN-γ和IL-2的水平。同时利用流式细胞术(flow cytometry,FCM)检测霉酚酸衍生物对T细胞IFN-γ和IL-2的分泌、表面分子CD25的表达以及增殖的影响。结果 2种霉酚酸衍生物对抗CD3刺激条件下诱导的小鼠脾细胞产生的IFN-γ和IL-2均具有浓度依赖性抑制作用,并且在抗CD3刺激的不同时间点分别加入2种霉酚酸衍生物均能不同程度地抑制小鼠脾细胞产生IFN-γ和IL-2;同时,与单独使用抗CD3刺激相比,分别加入10-5mol/L浓度的2种霉酚酸衍生物后,均能抑制小鼠T细胞表面分子CD25的表达以及增殖。结论体外实验表明2种霉酚酸衍生物均对小鼠T细胞免疫功能具有明显抑制作用,该研究提示这2种霉酚酸衍生物可以抑制自身免疫性疾病和移植排斥反应。

Derivatives of mycophenolic acid inhibit T cell-mediated immune function of Balb/c mouse

To study the effect of two derivatives of mycophenolic acid on T cell-mediated immune function of Balb/c mouse in vitro,the splenocytes of Balb/c mouse were cultured with anti-CD3 in the absence or presence of mycophenolic acid derivative at different concentrations or different time points.After stimulation for 48 h,the supernatants were harvested and detected for production of IFN-γ and IL-2 by enzyme-linked immunosorbent assay(ELISA).Furthermore,the production of IFN-γ and IL-2 was detected by flow cytometry(FCM) after the second stimulation.The expression of cell surface molecule CD25 and proliferation of mouse T cells were respectively examined by FCM after stimulation for 48 h and 72 h.We found that both of the derivatives of mycophenolic acid inhibited anti-CD3-induced IFN-γ and IL-2 production from splenocytes in a concentration dependent manner,and inhibited the production of the two cytokines in different level when added the two derivatives of mycophenolic acid at different time points.Furthermore,both of the derivatives could significantly inhibit the expression of CD25 and proliferation of mouse T cells at the concentration of 10-5 mol/L after incubation for 2-3 d compared to positive control group.As both of the derivatives of mycophenolic acid have the ability of inhibiting T cell-mediated immune function of Balb/c mouse in vitro,the two derivatives may used in inhibiting the autoimmunity disease and graft rejective reaction.