摘要
目的探讨CD28、CD40通路共刺激后淋巴细胞产生IL-2的变化及免疫抑制剂环孢素A(CsA)、雷帕霉素(RPM)及霉酚酸(MPA)对共刺激通路激活后淋巴细胞产生IL-2的影响。方法采用单克隆抗体与淋巴细胞表面CD3、CD28及CD40L分子结合产生相应刺激信号,根据刺激条件不同设组为:①单刺激及共刺激:A:CD3mAb单刺激;B:CD3mAb+CD28mAb共刺激:C:1CD3mAB+CD28mAb+CD40LmAb共刺激;D:CD3mAb+CD28mAb+CTLA4mAb共刺激。各单抗的终浓度均为100ng/ml。②CSA干预组:将终浓度为300ng/ml的CSA加入上述A、B、C、D四组。③RPM干预组:将终浓度为300ng/ml的RPM加入上述A、B、C、D四组。④MPA干预组:将终浓度为300ng/ml的MPA加入上述A、B、C、D四组。用ELISA法测定上述细胞培养上清中的IL2值。结果CD28、CD40通路刺激后淋巴细胞产生IL-2的水平均明显升高。抗CD3单抗+抗CD28单抗+抗CD40L单抗共刺激后,与抗CD3单抗+抗CD28单抗共刺激组相比,IL-2呈现下降趋势。CTLA4mAb所提供的信号使共刺激后IL-2的产生降低。三种免疫抑制剂CSA、RPM及MPA对共刺激后IL-2的产生均有抑制作用,CSA的抑制作用更为明显。CSA与CTLA4mAb的作用有协同作用。结论CD28共刺激通路在淋巴细胞活化中起着关键作用。CsA、RPM、MPA及抗CTLA4单抗对共刺激后IL-2的产生均有抑制作用,CSA的抑制作用更为明显。
Objective To investigate the (RPM), and Macophenolic acid (MPA) on the CO40 co-stimulated lymphocyte. Methods The effect of cyclosporin A (CsA),Rapamycin production of IL-2 produced by C028 and IL-2 production was examined By method of ELISA. The experimental groups were divided into ①mono- and co-stimulation: CD3 mAb mono-stimulation(group A); CD3mAb+CD28mAb co-stimulation (group B) ; CD3mAb+CD28mAb+CD40LmAb co-stimulation (group C ); CD3mAb+CD28mAb+CTLA4mAb co-stimulation (group D); ②CsA group: added 300ng/ml of CsA to group A, B, C, D; ③RPM group: added 300ng/ml of RPM to group A,B,C,D;④MPA group: added 300ng/ml of MPA to group A, B, C, D. Results The production of IL-2 produced by CD28 and CD40 co-stimulated lymphocyte was highly increased. CTLA4mAb as well as three immunosuppressants of CsA,RPM and MPA inhibited the IL-2 production of co-stimulated lymphocyte, and the inhibitory effect of CsA on IL-2 production was more significant. The co-inhibitory effect of CTLA4mAb and CsA was detected. Conclusions CD28 co-stimulatory pathway plays the key role in lymphocyte activation and IL-2 production. CsA, RPM and MPA can inhibite the IL- 2 production of co-stimulated lymphocyte. CsA and CTLA4mAb have co-inhibitory effect on the IL-2 production of co-stimulated lymphocyte.
出处
《国际医药卫生导报》
2007年第15期10-13,共4页
International Medicine and Health Guidance News
基金
深圳市科技计划资助项目(编号:JH200507131019A)