GITR抗体介导增强NK细胞杀伤活性的实验研究

GITR antibody enhancing the NK cells killing activity

目的探讨糖皮质激素诱导的TNF受体家族相关受体(glucocorticoid-inducedtumornecrosisfactorreceptorfamilyrelatedreceptor,GITR)的抗体通过抑制Treg细胞的功能,进而增强NK细胞杀伤活性来对L615白血病细胞产生杀伤作用。方法通过不同的给药方式将L615白血病小鼠设立为4个实验组,提取实验分组后的小鼠脾脏中NK细胞作为效应细胞,以L615白血病细胞作为靶细胞,在体外观察了NK细胞的杀伤活性变化情况,并运用RT-PCR,进一步观察了体现NK细胞杀伤活性的几个相关指标的变化。结果GITR抗体可以明显增强小鼠脾脏中NK细胞的杀伤活性,具体表现为同NK细胞活性密切相关的3个指标穿孔素(Perforin),γ干扰素(IFN-γ),Fas的表达量明显增加。结论GITR抗体能够通过Treg细胞的调节增强NK细胞的杀伤活性,进而有效的抑制L615白血病细胞。

Objective To explore how the antibody of glucocorticoid-induced tumor necrosis factor receptor （GITR） exerts inhibitory effect on the L615 leukemia cells by strengthening the activation of the NK cells. Methods The 24 established L615 leukemia mice were equally and randomly divided into 4 experimental groups according to different drugs given intraperitoneally, group Ⅰ （normal saline） , Ⅱ （GITR） , Ⅲ （cyclophosphamide） , and Ⅳ （ GITR ＋ eyelophosphamide）. Then the NK cells were extracted from the spleen of mice as effective cells, and L615 leukemia cells served as the target cells. The changes of the NK cells＇ killing activation was observed in vivo. The mRNA levels of 3 proteins tightly related to the NK cells＇activation Perforin, IFN-γ and Fas mRNAs were detected with RT-PCR. Results The GITR-antibody enhanced the killing activity of the NK cells obviously, with the expressions of the 3 proteins increasing obviously. Conclusion By regulation of the Treg cells, the GITR-antibody can inhibit the L615 leukemia cells through enhancing the NK cells＇ killing activity.