Chen Guanghua, Wu Depei, Wang Yi, Cen Jiannong, Feng Yufeng, Sun Aining, Tang Xiaowen, Chang Huirong, Zhu Ziling
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou, China.
Eur J Haematol. 2008 Sep;81(3):226-35. doi: 10.1111/j.1600-0609.2008.01108.x. Epub 2008 Jun 28.
Graft-versus-host disease (GVHD), leukemia relapse, and immune deficiency remain the major limitations of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor natural killer cells (NK) and cytokines have good potential in GVHD prevention and immune reconstitution enhancement. Improved survival after allo-HSCT therefore requires effective prophylaxis to reduce GVHD and strategy to mediate graft-versus-leukemia (GVL) effect. We studied the administration of expanded donor NK cell infusion and interleukin-2 (IL-2) and IL-15 mixture treatment in a murine allo-HSCT model for its effects on GVHD, immune reconstitution and leukemia relapse. In the GVHD model, recipient mice were reconstituted with bone marrow (BM) cells and splenocytes via vein. In the leukemia model, recipient mice were inoculated with EL9611 leukemia cells via vein 8 d prior to transplant. NK cell infusion mice group had lower clinical GVHD scores and suffered less severe GVHD-associated weight loss than control mice group. 90% of control mice died of leukemia relapse within 52 d post-transplant. NK cell infusion and IL-2 and IL-15 treatment recipient mice had improved survival compared with control mice. NK cell infusion and IL-2 and IL-15 treatment recipient mice had also accelerated lymphoid immune reconstitution compared with control mice group. Expanded donor NK cell infusion and IL-2 and IL-15 treatment could promote lymphoid immune reconstitution, mitigate GVHD, and reduce leukemia relapse in allo-HSCT recipients. The findings may have important significance for complication prevention in clinical allo-HSCT.
移植物抗宿主病（GVHD）、白血病复发和免疫缺陷仍然是异基因造血干细胞移植（allo-HSCT）的主要限制因素。供体自然杀伤细胞（NK）和细胞因子在预防GVHD和增强免疫重建方面具有良好的潜力。因此，提高allo-HSCT后的生存率需要有效的预防措施来减少GVHD，并采取策略介导移植物抗白血病（GVL）效应。我们在小鼠allo-HSCT模型中研究了输注扩增的供体NK细胞以及白细胞介素-2（IL-2）和IL-15混合物治疗对GVHD、免疫重建和白血病复发的影响。在GVHD模型中，通过静脉给受体小鼠输注骨髓（BM）细胞和脾细胞进行重建。在白血病模型中，在移植前8天通过静脉给受体小鼠接种EL9611白血病细胞。NK细胞输注小鼠组的临床GVHD评分较低，与对照组小鼠相比，GVHD相关的体重减轻也较轻。90%的对照小鼠在移植后52天内死于白血病复发。与对照小鼠相比，NK细胞输注以及IL-2和IL-15治疗的受体小鼠生存率有所提高。与对照组小鼠相比，NK细胞输注以及IL-2和IL-15治疗的受体小鼠的淋巴免疫重建也加速。扩增的供体NK细胞输注以及IL-2和IL-15治疗可促进allo-HSCT受体的淋巴免疫重建，减轻GVHD，并减少白血病复发。这些发现可能对临床allo-HSCT并发症的预防具有重要意义。
