雷帕霉素对人单核细胞来源的树突状细胞免疫功能的影响

目的：研究雷帕霉素对人树突状细胞（DC）免疫功能的影响。方法分离外周血单个核细胞,在含粒细胞巨噬细胞集落刺激因子（rhGM- CSF）、IL-4、胎牛血清及有或无雷帕霉素的培养条件下制备DC。用流式细胞仪检测DC表型（CD1a、CD83、CD86、HLA- DR）；混合淋巴细胞反应（MLR）检测DC对同种异体T淋巴细胞的刺激能力；流式细胞仪检测DC吞噬功能和凋亡细胞数；ELISA法测定MLR上清液中的细胞因子。结果与对照组比较,经雷帕霉素处理的DC表面CD1a、CD83、CD86、HLA- DR的表达明显降低（均P＜0.01）；对T淋巴细胞刺激的能力下降（P＜0.01）；细胞吞噬能力下降（P＜0.01）；凋亡细胞数增加（P＜0.01），MLR中细胞因子（TNF-α、IL-10、IL-12）浓度降低（均P＜0.01）。结论雷帕霉素对人树突状细胞免疫功能有明显的抑制作用,可能是其防止冠状动脉支架术后再狭窄的机制之一。

Effects of rapamycin on immune function of human monocyte-derived dendritic cells

Objective To investigate the effects of rapamycin on immune function of human monocyte- derived dendritic cel s （DC）. Methods Human monocytes were isolated and cultured with fetal bovine serum, granulocyte- macrophage colony- stimulating factor （rhGM- CSF） and interleukin- 4 （rhIL- 4） with or without rapamycin. Al ogeneic T cel activation by DCs was tested by mixed lymphocyte reaction （MLR）. ELISA was used to detect the expression of IL- 10, IL- 12 and TNF- α. The im-munophenotype, cel apoptosis and endocytic activity of DCs were measured by flow cytometry. Results The level of CD1a, CD83, CD86 and HLA- DR in rapamycin treatment group was lower than those in control group（P〈0.01）. Rapamycin inhibited the endocytic and T- cel stimulating activity of DCs （P〈0.01）, induced DC apoptosis, and decreased the secretion of IL- 10, IL- 12 and TNF- a（P〈0.01）. Conclusion Rapamycin can inhibit the immune function of human monocyte- derived dendritic cel s, which may be one of the mechanisms for prevention of in- stent restenosis.