Vα14iNKT细胞对异基因骨髓移植GVHD具有抑制作用

An elementary study on the suppression of Vα14iNKT cells on GVHD in allogeneic BMT

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。

To confirm that the adoptive transfer of in vitro-expanded donor Vα14iNKT can protect against acute GVHD following allogeneic bone marrow transplantation（BMT）. The in vitro Vα14iNKT cells were expanded with α-GalCer and IL-2 treatment. Acute GVHD model of C57BL/6DBA/2 was established, just as acute GVHD group. Based on this aGVHD model, donor Vα14iNKT were adoptive transferred, termed NKT-treated group. Then the survival, body weight, GVHD scoring, histopathological specimens, and serum cytokine analysis in the aGVHD group were compared with those in the NKT-treated groups. It was found that the in vitro, Vα14iNKT cells could produce large amounts of Th1 and Th2 cytokine rapidly after stimulation. The results of the mice models demonstrated that the symptoms of acute GVHD were effectively alleviated in the NKT-treated group, and the survival time in the NKT-treated group was significantly longer than that in aGVHD group. In addition, at 7 days after BMT, the levels of IL-4 were higher in mice with NKT treatment than in those without, but IFN -γ levels showed no significant difference between these two groups at this time. The results suggest that the allogeneic iNKT cells play an important role to inhibit acute GVHD by modulating the Th1/Th2 cytokine levels. These findings indicated the therapeutic potential of in vitro-expanded donor iNKT cells in protection against acute GVHD in allogeneic hematopoietic stem cell transplantation.