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关键词：骨髓移植；杀伤细胞，天然；移植物抗宿主病；移植物抗肿瘤效应
摘要 目的 研究供鼠的活化自然杀伤细胞(NK细胞)对小鼠异基因骨髓移植的影响。 方法 将荷瘤鼠照射后，于输注骨髓细胞(含T细胞)之前4小时或之后72小时，注射供鼠的活化NK细胞，观察荷瘤鼠CFU-S、CFU-GM、生存期、体重、病理组织学和双肺瘤结节等指标。结果 输注供鼠的活化NK细胞能显著促进荷瘤鼠CFU-S和CFU-GM增殖。输注骨髓细胞前4小时输注供鼠的活化NK细胞能显著提高荷瘤鼠生存率,减轻移植物抗宿主病(GVHD)的病理损伤程度，并使肺瘤结节数量减少；而输注骨髓细胞后72小时输注供鼠的活化NK细胞能显著加重GVHD病理损伤程度。结论 ①在小鼠异基因骨髓移植的初始阶段，输注供鼠的活化NK细胞能促进造血重建，预防GVHD并同时增强移植物抗肿瘤(GVT) 效应；输注骨髓细胞之后，输注供鼠的活化NK细胞则起到加重GVHD的不良作用；②GVT和GVHD是能够被分开的。
Effect of activated donor-type NK cells on allogeneic bone marrow transplantation in mice
SUN Kai , ZHANG Maohong, TIAN Zhigang, et al.
Department of Hematology,The Affiliated Hospital,Shandong Medical University,Jinan 250012
Abstract Objective To study the effect of activated donor-type NK cells on allogeneic bone marrow transplantation(BMT). Methods Four hours before or 72 hours after transfusing bone marrow cells(containing T cells),the activated donor-type NK cells were injected into tumor-bearing mice conditioned by irradiation. The effect of these NK cells were assessed by CFU-S,CFU-GM,survival,body weight,histopathology and lung metastases in the recipients. Results The transfusion of activated donor-type NK cells markedly increased CFU-S and CFU-GM numbers. When these NK cells were transfused 4 hours before BMT, they augmented GVT yet inhibited GVHD as evidenced by increases in survival duration and body weight, reduction in grade of histopathological changes and decrease in lung metastases. However,when activated donor-type NK cells were transfused 72 hours after BMT, they exacerbated GVHD. Conclusions The activated donor-type NK cells could prevent GVHD and produce significant GVT effects and also resulted in greater hematopoietic reconstitution if they were at the initial stage of allogeneic BMT in mice. Thereafter, the activated donor-type NK cells were detrimental and could exacerbate the subsequent GVHD, these results also demonstrated that GVT and GVHD could be dissociable phenomena.
Key words Bone marrow transplantation Killer cell, natural Graft-versus-host disease Graft-versus-tumor effect
在异基因骨髓移植(allo-BMT)中,多种免疫细胞及其释放的多种细胞因子参与的免疫反应,不仅影响骨髓植入和造血细胞的增殖,也决定着移植排斥反应和移植物抗宿主病(GVHD)的发生与否 ......
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