论文部分内容阅读
研究初步探讨了在同种异基因骨髓移植中过继性输注体外扩增的Vα14iNKT细胞对急性GVHD的抑制作用。小鼠脾细胞体外经α-GalCer和IL-2的联合刺激扩增得到Vα14iNKT细胞。建立C57BL/6→DBA/2小鼠急性GVHD模型,即急性GVHD组。在此模型基础上,过继性输注供鼠Vα14iNKT细胞,即实验组。对各组受鼠GVHD发病情况、相关病理学检查、生存情况及血清中Th1/Th2型细胞因子的变化情况进行比较。结果是在体外刺激下,Vα14iNKT细胞能分泌Th1/Th2型细胞因子。体内实验发现,与急性GVHD组相比,实验组受鼠在移植后GVHD各项病症明显减轻,生存期显著延长。另外,通过对血清中细胞因子的测定发现,在骨髓移植后第7天,实验组IL-4分泌量显著高于急性GVHD组;而IFN-γ水平无显著性差异。表明体外诱导的供者Vα14iNKT细胞能通过调节Th1/Th2型细胞因子的产生有效地抑制急性GVHD。这为体外扩增的供者iNKT抑制GVHD的作用机制及NKT细胞疗法的临床运用提供了新的思路。
This study initially explored the inhibitory effect of Vα14iNKT cells expanded by adoptive transfusion in vitro on acute GVHD in allogeneic bone marrow transplantation. Vα14iNKT cells were obtained from mouse splenocytes stimulated with α-GalCer and IL-2 in vitro. Acute GVHD model of C57BL / 6 → DBA / 2 mice was established, namely acute GVHD group. Based on this model, adoptive infusion was performed on Vα14iNKT cells, the experimental group. The incidence of GVHD in each group, pathological examination, survival and changes of serum Th1 / Th2 cytokines were compared. The result is that Vα14iNKT cells can secrete Th1 / Th2 type cytokines under in vitro stimulation. In vivo experiments found that, compared with the acute GVHD group, the mice in the experimental group after GVHD significantly reduced the incidence of various diseases, significantly prolonged survival. In addition, the determination of cytokines in serum found that on the 7th day after bone marrow transplantation, the secretion of IL-4 in the experimental group was significantly higher than that of the acute GVHD group; however, there was no significant difference in the level of IFN-γ. The results showed that in vitro induced Vα14iNKT cells could effectively inhibit acute GVHD by regulating the production of Th1 / Th2 cytokines. This provides a new idea for the mechanism of iNKT inhibiting GVHD in vitro and the clinical application of NKT cell therapy.