供鼠的活化自然杀伤细胞对小鼠异基因骨髓移植的影响

Effect of activated donor type NK cells on allogeneic bone marrow transplantation in mice

目的 研究供鼠的活化自然杀伤细胞（ Ｎ Ｋ 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 Ｎ Ｋ 细胞，观察荷瘤鼠 Ｃ Ｆ Ｕ Ｓ、 Ｃ Ｆ Ｕ Ｇ Ｍ、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 Ｎ Ｋ细胞能显著促进荷瘤鼠 Ｃ Ｆ Ｕ Ｓ和 Ｃ Ｆ Ｕ Ｇ Ｍ 增殖。输注骨髓细胞前４ 小时输注供鼠的活化 Ｎ Ｋ 细胞能显著提高荷瘤鼠生存率，减轻移植物抗宿主病（ Ｇ Ｖ Ｈ Ｄ） 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 Ｎ Ｋ 细胞能显著加重 Ｇ Ｖ Ｈ Ｄ 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 Ｎ Ｋ 细胞能促进造血重建，预防 Ｇ Ｖ Ｈ Ｄ 并同时增强移植物抗肿瘤（ Ｇ Ｖ Ｔ） 效应；输注骨髓细胞之后，输注供鼠的活化 Ｎ Ｋ 细胞则起到加重 Ｇ Ｖ Ｈ Ｄ 的不良作用；② Ｇ Ｖ Ｔ和 Ｇ Ｖ Ｈ Ｄ 是能够被分开的。

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.