Prlic Martin, Kamimura Daisuke, Bevan Michael J
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle , WA 98195-7370, USA.
Blood. 2007 Sep 15;110(6):2024-6. doi: 10.1182/blood-2007-04-086108. Epub 2007 Jun 6.
Bone marrow transplants are an important therapeutic tool for treating certain types of cancer as well as genetic diseases affecting the hematopoietic system. Until the transferred stem cells differentiate and reconstitute the immune system, recipients are at increased risk from opportunistic infections. We report the rapid generation of a functional natural killer (NK) compartment in lethally irradiated mice that received bone marrow cells from a syngeneic donor by treatment with IL-2/anti-IL-2 antibody complexes. We demonstrate that IL-2 complexes specifically expand the donor but not the host NK population and discuss the implications of this finding in the context of graft-versus-host disease and tumor relapse. Finally, we show that NK cells rapidly generated by IL-2 complexes kill MHC class I-deficient cells effectively in vivo. These data underline the unique therapeutic potential of IL-2 complexes.
骨髓移植是治疗某些类型癌症以及影响造血系统的遗传疾病的重要治疗手段。在移植的干细胞分化并重建免疫系统之前,接受者面临机会性感染的风险增加。我们报告了在接受同基因供体骨髓细胞的致死性照射小鼠中,通过用白细胞介素-2(IL-2)/抗IL-2抗体复合物治疗,快速产生功能性自然杀伤(NK)细胞区室。我们证明IL-2复合物特异性地扩增供体而非宿主NK细胞群体,并在移植物抗宿主病和肿瘤复发的背景下讨论这一发现的意义。最后,我们表明由IL-2复合物快速产生的NK细胞在体内能有效杀伤MHC I类缺陷细胞。这些数据强调了IL-2复合物独特的治疗潜力。