OX40调控双阴性T细胞的转化及抑制功能研究

Study on the conversion and immune suppressive function of double negative T cells regulated by OX40

目的探讨免疫共刺激分子OX40对双阴性T细胞(DN T细胞)转化、抑制功能的影响及可能的作用机制。方法通过中和抗体及基因敲除的方式将OX40作用阻断,检测在这一过程中DN T细胞的转化效率、抑制功能的变化及OX40对DN T细胞存活的影响。结果通过DN T细胞的转化实验发现,将OX40阻断,DN T细胞的转化效率分别从20.2%、29.1%降为10.5%、15.9%。同时与CD4 T细胞相比,OX40在DN T细胞中高表达,其阳性率为27.0%。通过DN T细胞的体外抑制实验发现,OX40敲除后的DN T对CD4 T细胞的抑制作用明显减弱。通过Annexin V染色发现,OX40敲除后DN T细胞的凋亡率分别从14.6%、22.3%增加为21.1%、35.1%,同时OX40敲除使DN T细胞抗凋亡基因表达降低。结论 OX40敲除能降低DN T细胞的转化效率,减弱其对CD4 T细胞抑制功能,这有可能与OX40敲除所致DN T细胞凋亡增加有关。

Objective To explore the effect of 0X40 on conversion and immune suppressive function of double negative T （DN T） cells, and the possible mechanism of these functions. Methods The signal of OX40/OX40L was blocked by neutralization of antibody and gene knock-out ,and the efficiency of conversion of DN T cells, the inhibitory function and the effect of 0X40 on survival of DN T cells were detected. Results The efficiency of conversion of DN T cells had been reduced from 20. 2% - 29 .1% to 10. 5% ？15. 9% respectively when 0X40 was knocked out. OX40 was highly expressed in converted DN T cells with a positive rate of 27. 0% compared with CD4 T cells. 0X40 deficient DN T cells showed significantly reduced inhibition on the proliferation of CD4 T cells. The rate of apoptotic DN T cells was increased from 14. 6% - 22. 3% to 21.1 % -35.1 % respectively through Annexin V staining assays. Conclusion Knockout of 0X40 can reduce the efficiency of conversion of DN T cells and lower its suppressive function, which may be related to the increase of apoptosis of DN T cells.