Zeis M, Uharek L, Glass B, Steinmann J, Dreger P, Gassmann W, Schmitz N
Department of Internal Medicine II, University of Kiel, Germany.
Br J Haematol. 1997 Mar;96(4):757-61. doi: 10.1046/j.1365-2141.1997.d01-2101.x.
Allogeneic lymphocytes administered with an unmanipulated bone marrow transplant provide a strong antileukaemic effect, the so-called graft-versus-leukaemia (GVL) effect. On the other hand, T-cell-mediated graft-versus-host-disease (GVHD) observed after transplantation of unmanipulated BM graft causes substantial morbidity and mortality. The aim of the present study was to determine the antileukaemic potential of enriched IL-2 activated NK cells administered 2 h after BMT. Balb/c (H-2d) mice were given a dose of A20 (H-2d, B-cell leukaemia) cells 2 d prior to lethal total body irradiation (TBI) and transplantation of either syngeneic or allogeneic anti-Thy1.2 (CD90) depleted bone marrow cells. Either syngeneic (Balb/c, H-2d) or allogeneic (C57BL/6, H-2b) enriched and IL-2 (200 U/ml for 24 h) activated NK cells were given 2 h after BMT. Injection of A20 leukaemia into normal Balb/c recipients led to death after a median of 14 d. A lethal dose of TBI followed by either syngeneic or allogeneic Thy1.2-depleted BMT resulted in a modest antileukaemic effect. The adoptive transfer of syngeneic enriched and IL-2 preincubated NK cells given at time of BMT exerted a significantly better GVL effect. However, the infusion of allogeneic enriched NK cells resulted in a stronger GVL effect. These results clearly demonstrate that allogeneic NK cells are superior to syngeneic NK cells in their potential to eradicate residual leukaemia cells after BMT without mediating clinical overt GVHD. This experimental setting may offer a strategy for treatment of haematological malignancies in a phase of minimal residual disease.
与未处理的骨髓移植一同给予的同种异体淋巴细胞可产生强大的抗白血病效应，即所谓的移植物抗白血病（GVL）效应。另一方面，未处理的骨髓移植物移植后观察到的T细胞介导的移植物抗宿主病（GVHD）会导致相当高的发病率和死亡率。本研究的目的是确定在骨髓移植后2小时给予富集的IL-2激活的自然杀伤细胞（NK细胞）的抗白血病潜力。在致死性全身照射（TBI）和移植同基因或同种异体抗Thy1.2（CD90）耗尽的骨髓细胞前2天，给Balb/c（H-2d）小鼠接种一剂A20（H-2d，B细胞白血病）细胞。在骨髓移植后2小时给予同基因（Balb/c，H-2d）或同种异体（C57BL/6，H-2b）富集且经IL-2（200 U/ml，处理24小时）激活的NK细胞。向正常Balb/c受体注射A20白血病细胞后，中位14天后导致死亡。致死剂量的TBI后进行同基因或同种异体Thy1.2耗尽的骨髓移植产生了适度的抗白血病效应。在骨髓移植时给予同基因富集且经IL-2预孵育的NK细胞的过继转移产生了明显更好的GVL效应。然而，输注同种异体富集的NK细胞产生了更强的GVL效应。这些结果清楚地表明，同种异体NK细胞在骨髓移植后根除残留白血病细胞的潜力方面优于同基因NK细胞，且不会介导明显的临床GVHD。这种实验设置可能为微小残留病阶段的血液系统恶性肿瘤治疗提供一种策略。
