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目的探索建立移植后淋巴组织增生性疾病(PTLD)动物模型的方法。方法将40名EB病毒(EBV)阳性志愿者的外周血淋巴细胞(huPBL)分别经腹腔注射入3只联合免疫缺陷动物即SCID小鼠体内,通过血液人免疫球蛋白(IgG)的测定,确定人类免疫细胞在小鼠体内的重建。在小鼠濒死或死亡后取出肿瘤组织,通过组织病理切片和免疫组化的分析方法确定淋巴增生性疾病(LPD)的产生及其细胞来源。结果移植huPBL后8周和12周SCID小鼠血清中人IgG含量分别达到(750.0±13.2)μg/mL和(1 050.0±14.6)μg/mL。濒死或死后,组织病理切片显示为伴有高度有丝分裂率的大细胞淋巴瘤,肿瘤CD20阳性,LMP-1阳性。在40名志愿者中,10例在8周后产生LPD(25%),SCID小鼠的中位成瘤率为100%;8例在10~16周出现LPD(20%),中位成瘤率为55%;其他22例(55%)在16周后仍无LPD产生。结论SCID小鼠腹腔注射EB病毒阳性的人类外周血白细胞可建立PTLD的动物模型。
Objective To explore a method to establish an animal model of post-transplant lymphoproliferative disease (PTLD). Methods Peripheral blood lymphocytes (huPBLs) from 40 EBV-positive volunteers were injected intraperitoneally into 3 SCID mice with immunodeficient animals, and their blood levels of human immunoglobulin (IgG) were determined Reconstruction of human immune cells in mice. Tumor tissues were removed after the mice had died or died, and the production of lymphoproliferative disease (LPD) and its cellular origin were determined by histopathological analysis and immunohistochemical analysis. Results Serum IgG levels of SCID mice reached (750.0 ± 13.2) μg / mL and (1050.0 ± 14.6) μg / mL at 8 and 12 weeks after transplantation of huPBL. After dying or death, histopathology showed a large cell lymphoma with a high rate of mitosis, which was positive for CD20 positive and LMP-1 positive. Among the 40 volunteers, 10 developed LPD (25%) after 8 weeks and the median tumor formation rate in SCID mice was 100%. Eight developed LPD (20%) at 10 to 16 weeks, with median The tumor rate was 55%; the other 22 patients (55%) still had no LPD after 16 weeks. Conclusion The animal model of PTLD can be established by intraperitoneal injection of Epstein-Barr virus positive human peripheral blood leucocytes in SCID mice.