TBI及环磷酰胺选择性去除同种异基因反应 供者淋巴细胞探究.docVIP

TBI及环磷酰胺选择性去除同种异基因反应 供者淋巴细胞探究 　 ; 作者：陈宝安，董伟民, 丁家华，孙雪梅，邓晓静, 张琰，毕延智 毕业论文 赵刚, 高冲，孙耘玉，王骏，程坚，Schmitt M2 ，Schmitt A2 毕业论文 【摘要】; 　　本研究用全身照射(TBI)和环磷酰胺（CY）选择性去除同种异基因反应的供者淋巴细胞,为预防移植物抗宿主病(GVHD)的发生探索新的手段。以(BALB/c×C57BL/6)F1雌性小鼠（H?2d/b）为受鼠，于第0天接受亚致死量的60Co?γ射线全身照射，总剂量为4 Gy，第1天接种P388D1白血病细胞，第2天输注由C57BL／6雄性小鼠（H?2b）为供鼠提供的MHC不匹配的供者脾淋巴细胞，在造血干细胞移植前诱导移植物抗白血病效应（GVL）。第6天腹腔注射环磷酰胺（CY）200 mg/kg或再次TBI 9 Gy，选择性去除同种异基因反应供者淋巴细胞，第7天输注(BALB/c×C57BL/6)F1雄性小鼠（H?2d/b）提供的骨髓造血干细胞。结果显示：以CY和TBI选择性去除同种异基因反应供者淋巴细胞组的小鼠无白血病和GVHD的发生，生存期超过了210天，于移植后第21天出现完全供者嵌合，然后嵌合率下降，第90天表现为混合嵌合体（MC）。对照组的小鼠出现了白血病和GVHD，出血、感染明显，生存期短，为20-36天（Plt;0.01）。结论：同基因骨髓移植前输注不相匹配的供者脾细胞诱导GVL效应,然后再通过TBI和CY选择性去除同种异基因反应的供者淋巴细胞来预防移植物抗宿主病(GVHD)的发生是可能的。 毕业论文 【关键词】; 同种异基因造血干细胞移植；同种异基因反应供者淋巴细胞；移植物抗白血病效应；移植物抗宿主病；全身照射；环磷酰胺 毕业论文 　　Selective Elimination of Alloreactive Donor Lymphocytes by Using TBI and Cyclophosphamide 毕业论文 Abstract ; This study was aimed to investigate a new method of avoiding graft?vs?host disease (GVHD); through selective elimination of alloreactive donor lymphocytes by using total body irradiation (TBI) and cyclophosphamide (Cy). Female (BALB/c×C57BL/6)F1 mice (H?2d/b) as recipients received 60Co γ?ray sublethal TBI; of 4 Gy on day 0 followed by being inoculated with P388D1 leukemia cell line on day 1,injection of allogeneic splenocytes from; C57BL／6 male mice（H?2b） was carried out for induction of graft?vs?leukemia (GVL) effect prior to stem cell transplantation (SCT) , intraperitoneally injection of cyclophosphamide (Cy) (200 mg/kg) and TBI (9 Gy) was given on day 6. One day later, treated mice were rescued with; bone marrow hematopoietic stem cells from; (BALB/c×C57BL/6)F1 male mice（H?2d/b）. The results showed that recipients had no occurrence of leukemia and GVHD through; selective elimination of alloreactive donor lymphocytes by Cy and TBI, survived more than 210 days，the complete?donor chimerism occured on day 21 after transplantation. The ratio of chimerism descended subsequently, but still displayed mi