髓样抑制细胞免疫抑制机理的研究

Study on mechanisms of immune suppression mediated by myeloid derived suppressor cells

目的:研究荷瘤小鼠来源的髓样抑制细胞(Myeloid derived suppressor cell,MDSC)在肿瘤免疫抑制中的作用机理。方法:用Percoll分离法从荷瘤小鼠的脾脏和骨髓中分离Gr-1+CD11b+MDSC;用流式细胞术检测MDSC对T细胞增殖的抑制作用;分别用生化法和ELISA技术检测MDSC体外培养上清中抑制性因子NO、ROS和IL-10、TGF-β的含量。结果:MDSC在荷瘤小鼠的脾脏和骨髓中聚集增多,且其在骨髓中所占的比例显著高于脾脏;MDSC可以明显抑制脾脏细胞的增殖,体外培养6小时的MDSC可以分泌大量NO、ROS和IL-10、TGF-β。结论:本实验进一步证实MDSC可以通过分泌大量NO、ROS和IL-10、TGF-β抑制T细胞增殖。

Objective：To study the mechanisms of immune suppression mediated by Gr-1 ＋ CD11b ＋ myeloid derived suppressor cells （Gr-1 ＋ CD11b＋ MDSC） from tumor-bearing mice. Methods： Gr-1＋ CD11b＋ MDSC recruited into spleen and bone marrow of tumor-bearing mice were purified by Percoll, and suppression mediated by MDSC on T cell proliferation from spleen of naive mice was detected by flow cytometry with CSFE and FITC-anti CD3 staining, and NO, ROS, IL-10 and TGF-β in the supernatant of MDSC were detected by Griess and ELISA. Results：There were much more Gr-1＋ CD11b＋ MDSCs in spleen and bone marrow from tumor-bearing mouse than those of naive mouse,and suppression on T cell proliferation mediated by MDSC from tumor bearing mouse was significantly increased, and there were much more NO, ROS,IL-10 and TGF-β in the supernatant of these MDSC than that from naive mouse. Conclusion： MDSC from tumor-bearing mice secreted high level of NO,ROS,IL-10 and TGF-β to induce immune suppression,and inhibite the proliferation of T cells.