Donor NK Cells and IL-15 Promoted Engraftment in Nonmyeloablative Allogeneic Bone Marrow Transplantation
Donor NK Cells and IL-15 Promoted Engraftment in Nonmyeloablative Allogeneic Bone Marrow Transplantation
复制标题
供体 NK 细胞和 IL-15 促进非清髓性同种异体骨髓移植中的植入
DOI：
10.4049/jimmunol.1103199
复制
发表时间：
2012-08-15
影响因子：
4.4
通讯作者：
Liu, Haiyan
中科院分区：
文献类型：
--
作者：
Hu, Bo;Bao, Guangming;Liu, Haiyan
在异基因骨髓移植（allo-BMT）中，供体NK细胞可以通过抑制宿主反应性来促进植入。IL-15可显著增强NK细胞的生物学活性。目前的研究试图评估供体NK细胞和IL-15给药对小鼠非清髓性allo-BMT模型植入和免疫重建的影响。在非清髓性allo-BMT过程中，输注供体NK细胞并用IL-15治疗的小鼠与单独治疗相比，供体植入增加。联合治疗的受体小鼠脾脏中供体来源的细胞亚群的数量也增加。供体NK细胞输注和IL-15处理的受体小鼠对供体型Ags的同种异体反应性显著降低，表现为MLR中受体小鼠脾细胞对供体型Ags的应答增殖和IL-2分泌减少，以及脾细胞杀伤供体型肿瘤靶标的能力降低。随后，我们将受体小鼠暴露于减少的辐射条件下，并表明供体NK细胞输注和流体动力学注射介导的IL-15表达可以协同促进供体移植，并抑制非清髓性allo-BMT期间的同种异体反应性。输注CFSE标记的供体CD45.1+ NK细胞证明IL-15可以增强输注的供体NK细胞的增殖和功能。IL-15治疗也促进了供体骨髓来源的NK细胞的发育和功能。因此，供体NK细胞输注和IL-15治疗可以协同促进小鼠非清髓性allo-BMT模型中供体来源细胞亚群的植入和发育，并抑制宿主同种异体反应。
Donor NK cells could promote engraftment by suppressing host alloreactive responses during allogeneic bone marrow transplantation (allo-BMT). The biological activity of NK cells could be significantly enhanced by IL-15. The current study attempted to evaluate the effect of donor NK cells and IL-15 administration on engraftment and immune reconstitution in a murine nonmyeloablative allo-BMT model. Mice infused with donor NK cells and treated with IL-15 during nonmyeloablative allo-BMT resulted in increased donor engraftment compared with either treatment alone. The number of donor-derived cell subsets also increased in the spleen of the recipient mice with combination treatment. The alloreactivity to donor type Ags was significantly reduced in the recipient mice with donor NK cell infusion and IL-15 treatment, which was manifested by decreased proliferation and IL-2 secretion of splenocytes from recipient mice in response to donor type Ags in MLR and decreased capacity of the splenocytes killing donor type tumor targets. We subsequently exposed recipient mice to reduced irradiation conditioning and showed that donor NK cell infusion and hydrodynamic injection-mediated IL-15 expression could synergistically promote donor engraftment and suppress alloreactivity during nonmyeloablative allo-BMT. Infusion of CFSE-labeled donor CD45.1+ NK cells demonstrated that IL-15 could enhance the infused donor NK cell proliferation and function in vivo. IL-15 treatment also promoted donor bone marrow-derived NK cell development and function. Thus, donor NK cell infusion and IL-15 treatment could synergistically promote the engraftment and the development of donor-derived cell subsets and suppress the host alloresponse in a murine nonmyeloablative allo-BMT model.