Li Ailing, Jiang Jiyang, Zhang Qingyin, Hao Jie, Xie Shusheng
Department of Immunology, Peking University Health Science Center, Beijing, China.
Immunol Lett. 2005 May 15;98(2):216-24. doi: 10.1016/j.imlet.2004.11.018. Epub 2004 Dec 15.
Impaired immune reconstitution following allogeneic T-cell depleted bone marrow transplantation (allo-TCD-BMT) is a major obstacle to its clinical application. Stromal cell line QXMSC1, established from bone marrow cells of BALB/c(H-2d), was transfected with murine IL-3 and/ or IL-2 gene, and injected into lethally irradiated C57BL/6(H2b) mice. We evaluated its effects on immunologic and hematopoietic reconstitution after allo-TCD-BMT. The results showed that QXMSC1-IL-3 + IL-2 could significantly increase the numbers of hematopoietic primitive progenitors (CFU-S), committed progenitors (CFU-GM, and BFU-E), and lymphocytes (CD8+ cells, CD4+ cells, and B cells). Similarly, immune functions of recipient mice were significantly enhanced in the QXMSC1-IL-3 + IL-2 group. In addition, QXMSC1-IL-3 or QXMSC1-IL-2 also exerted apparent effects on accelerating immune reconstitution, but these effects were far less than that of QXMSC1-IL-3 + IL-2. Our results demonstrated that stromal cell-mediated IL-3 and IL-2 gene therapy may be a potent approach in promoting immunologic and hematopoietic reconstitution after allo-TCD-BMT.
异基因T细胞去除的骨髓移植(allo-TCD-BMT)后免疫重建受损是其临床应用的主要障碍。从BALB/c(H-2d)骨髓细胞建立的基质细胞系QXMSC1用小鼠IL-3和/或IL-2基因转染,并注射到经致死剂量照射的C57BL/6(H2b)小鼠体内。我们评估了其对allo-TCD-BMT后免疫和造血重建的影响。结果显示,QXMSC1-IL-3 + IL-2可显著增加造血原始祖细胞(CFU-S)、定向祖细胞(CFU-GM和BFU-E)以及淋巴细胞(CD8+细胞、CD4+细胞和B细胞)的数量。同样,在QXMSC1-IL-3 + IL-2组中,受体小鼠的免疫功能显著增强。此外,QXMSC1-IL-3或QXMSC1-IL-2对加速免疫重建也有明显作用,但这些作用远小于QXMSC1-IL-3 + IL-2。我们的结果表明,基质细胞介导的IL-3和IL-2基因治疗可能是促进allo-TCD-BMT后免疫和造血重建的有效方法。