不同供受体T细胞比例对异基因造血干细胞移植后GVHD严重程度影响的实验研究

背景与目的:异基因造血干细胞移植研究近年来获重大进展,为恶性血液病的治愈提供了可能。移植物抗宿主病(graft-versus-hostdisease,GVHD)是异基因造血干细胞移植后的主要并发症,死亡率超过30%。临床发现植入是否成功及GVHD的严重程度与预处理后供受体T细胞比例有关。本研究建立大鼠异基因骨髓移植模型,探讨供受体的不同T细胞比例对GVHD严重程度的影响。方法:受体SD大鼠接受大剂量全身照射(totalbodyirradiation,TBI)加环磷酰胺(cyclophosphamideCTX)预处理,分别按1∶1、2∶1、4∶1的移植物与受体T细胞比例回输供体Wistar大鼠骨髓细胞,观察受体生存期、临床及病理GVHD评分。结果:实验组大鼠按移植物与受体T细胞比例为1∶1、2∶1和4∶1移植时,小鼠的存活时间分别为(16.7±1.3)天、(16.8±1.5)天和(15.0±1.7)天;临床GVHD评分分别为(2.4±0.6)分、(3.3±1.2)分和(5.3±1.4)分。移植物与受体T细胞比例为1∶1、2∶1移植时小鼠的存活时间、临床及病理GVHD评分与4∶1时比较有显著性差异(P<0.05)。结论:移植物内T细胞和经预处理后受体残存T细胞比例为1∶1、2∶1时,GVHD程度较轻;4∶1时,GVHD明显加重。

Experimental research on effects of different T cell ratios of graft to receptor on severity of GVHD after allo-stem cell transplantation

BACKGROUND & OBJECTIVE: Allogeneic stem cell transplantation has achieved great progress in hematology, and provided possibility to cure malignant hematological diseases. Graft-versus-host disease (GVHD) is a significant complication after transplantation with a mortality of over 30%. In clinical practice we noticed that the successful implantation and the severity of GVHD were associated with T cell ratio of graft to receptor after pretreatment. This study was to set up rat allo-stem cell transplantation model, and explore effects of different T cell ratios of graft to receptor on severity of GVHD. METHODS: SD rats were selected as receptor, and pretreated with total body irradiation (TBI), and cyclophosphamide (CTX). WISTAR rats were used as donors, their bone marrow cells were collected as graft. Receptors were transfused with different ratios of T cells (1:1, 2:1, and 4:1). Life-span, clinical and pathologic GVHD scores were observed. RESULTS: When T cell ratios of graft to receptor were 1:1, 2:1, and 4:1, life-spans of receptors were (16.7+/-1.3) d, (16.8+/-1.5) d, and (15.0+/-1.7) d, respectively; clinical GVHD scores of receptors were 2.4+/-0.6, 3.3+/-1.2, and 5.3+/-1.4, respectively. Life-span, and clinical and pathologic GVHD scores of receptors transfused with T cells of 1:1 and 2:1 were significantly different from those of receptors transfused with T cells of 4:1(P<0.05). CONCLUSION: When T cell ratio of graft to receptor was 1:1, or 2:1, the GVHD was comparatively mild; when this ratio reached to 4:1, the GVHD was aggravated.