髓样抑制细胞免疫抑制机理的研究

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。

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

Objective:To study the mechanisms of immune suppression mediated by Gr-1+CDllb+ myeloid derived suppressor cells (Gr-1~+CDllb~+MDSC)from tumor-bearing mice.Methods:Gr-1~+CDllb~+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 FTTC-anti CD3 staining,and NO,ROS,IL-10 and TGF-β in the supematant of MDSC were detected by Griess and ELISA.Results:There were much more Gr-1~+CDllb~+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 beating mouse was significantly increased,and there were much more NO,ROS,IL-10 and TGF-βin the supematant of these MDSC than that from naive mouse.Conclusion:MDSC from tumor-bearing mice secreted hish level of NO,ROS,IL-10 and TGF-βto induce immune suppression,and inhibite the proliferation of T cells.