CD28通路共刺激对淋巴细胞产生趋化因子 RANTES的影响

目的探讨CD28通路共刺激对淋巴细胞产生趋化因子RANTES的影响与意义,以及免疫抑制剂环孢素(CsA)对RANTES产生的抑制作用.方法分离健康人外周静脉血中的淋巴细胞,实验分为4组①抗CD3单克隆抗体(mAb)刺激组;②抗CD28mAb刺激组;③抗CD3mAb+抗CD28mAb共刺激组,即CD28共刺激组;④未加任何刺激作为对照组.吡咯啉烷二甲基硫脲(PDTC)和CsA以不同终浓度干预CD28共刺激组.采用ELISA法测定培养上清中RANTES含量,流式细胞术检测淋巴细胞CD25和RANTES受体CCR5表达率.结果培养48 h后,CD28共刺激组RANTES产生显著增加(P＜0.05);不同剂量PDTC和CsA对CD28共刺激后淋巴细胞产生RANTES均具有抑制作用;CD28共刺激后淋巴细胞CD25表达率显著增高(P＜0.05),而CCR5表达率显著降低(P＜0.05).结论CD28通路共刺激后淋巴细胞产生RANTES显著增加.淋巴细胞产生RANTES及其对RANTES的反应均受到CD28共刺激信号调控.核因子(NF)-κB的特异性抑制剂PDTC和免疫抑制剂CsA均可抑制淋巴细胞产生RANTES.

The Effect of Costimulation of CD28 Pathway on the RANTES Produced by Activated Lymphocytes

Objective:To investigate the effect of costimulation of CD28 pathway on the RANTES level produced by activated lymphocytes and on inhibition of Cyclosporin A(CsA). Methods: Human peripheral lymphocytes separated by Ficoll's liquor were divided into four groups:anti-CD3mAb group,anti-CD28mAb group,CD28 costimulation group and control group CD28 costimulation group was treated by different concentrations of Pyrrolidine dithiocarbamate (PDTC) or CsA. RANTES levels were detected by ELISA and the expression of CD25 and CCR5 in lymphocytes were detected by flow cytometry (FCM). Results: RANTES concentration was significantly higher in CD28 costimulation group than other groups(P<0.05). RANTES secreted by lymphocytes could be inhibited by PDTC or CsA. The expression of CD25 in lymphocytes was significantly increased after costimulation of CD28 pathway while CCR5 was significantly decreased(P<0.05). Conclusion: CD28 costimulation of CD28 pathway has an effect on RANTES produced by lymphocytes.The secretion of RANTES may be inhibited by PDTC or CsA.