Li A, Zhang Q, Jiang J, Yuan G, Feng Y, Hao J, Li C, Gao X, Wang G, Xie S
Department of Immunology, Peking University Health Center, Beijing, People's Republic of China.
Gene Ther. 2006 Aug;13(15):1178-87. doi: 10.1038/sj.gt.3302741. Epub 2006 Apr 6.
Allogeneic bone marrow transplantation (allo-BMT) is followed by a period of profound immune deficiency, which results in significant susceptibility to infections and limits the extensive application of this approach in clinic. Here, we transduced human interleukin-7 (IL-7) gene into donor-derived bone marrow stromal cells (MSCs) using adenovirus vector, and transplanted this gene-engineered MSCs (MSC-IL-7) into lethally irradiated C57BL/6 mice to investigate their effects on immune reconstitution following allo-BMT. Recipient mice receiving MSC-IL-7 cells plus T-cell-depleted bone marrow cells of BALB/c mice showed a significant increase in thymopoiesis and homeostatic expansion of peripheral T lymphocytes. Furthermore, injection of MSC-IL-7 cells following allo-BMT protected the host from the lethality caused by acute graft-versus-host disease (GVHD) and prevented the occurrence of GVHD induced by transplanted T cells. Thus, the use of MSC-IL-7 cells may be therapeutically useful for enhancing immune reconstitution without aggravating GVHD in allo-BMT mice.
异基因骨髓移植(allo-BMT)后会经历一段严重免疫缺陷期,这导致机体对感染高度易感,并限制了该方法在临床上的广泛应用。在此,我们使用腺病毒载体将人白细胞介素-7(IL-7)基因转导至供体来源的骨髓基质细胞(MSC)中,并将这种基因工程化的MSC(MSC-IL-7)移植到经致死剂量照射的C57BL/6小鼠体内,以研究其对allo-BMT后免疫重建的影响。接受MSC-IL-7细胞加BALB/c小鼠去除T细胞的骨髓细胞的受体小鼠,其胸腺生成和外周T淋巴细胞的稳态扩增显著增加。此外,allo-BMT后注射MSC-IL-7细胞可保护宿主免受急性移植物抗宿主病(GVHD)致死,并防止移植T细胞诱导的GVHD发生。因此,使用MSC-IL-7细胞可能在治疗上有助于增强allo-BMT小鼠的免疫重建,而不加重GVHD。