Mouse host unlicensed NK cells promote donor allogeneic bone marrow engraftment
Mouse host unlicensed NK cells promote donor allogeneic bone marrow engraftment
复制标题
小鼠宿主未经许可的 NK 细胞促进供体同种异体骨髓移植
DOI：
10.1182/blood-2015-08-665570
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发表时间：
2016-03-03
期刊：
影响因子：
20.3
通讯作者：
Murphy, William J.
中科院分区：
文献类型：
--
作者：
Alvarez, Maite;Sun, Kai;Murphy, William J.
自然杀伤（NK）细胞作为基于识别主要组织相容性复合体I（MHCI）分子的抑制性受体表达的亚群存在。携带自身MHCI的MHCI结合受体的NK细胞亚群已被称为“许可的”，并表现出更高的响应刺激的能力。在骨髓移植（BMT）的背景下，宿主许可NK（L-NK）细胞也已被证明是负责在致死辐射后小鼠中同种异体和MHCI缺陷型BM细胞（BMC）的急性排斥反应。然而，受体非许可NK（U-NK）细胞的作用尚未得到很好的确定，关于同种异体BMC抗性。在NK细胞刺激后，与未处理组相比，先前耗尽宿主L-NK细胞导致供体植入显著增加。令人惊讶的是，这种增加的供体植入在总宿主NK细胞耗尽后减少，表明U-NK细胞实际上可以促进供体同种异体BMC植入。此外，U-NK细胞与同种异体而非同基因BMCs直接共培养导致体外集落形成单位细胞生长增加，这至少部分由粒细胞巨噬细胞集落刺激因子（GM-CSF）产生介导。这些数据表明，宿主NK细胞亚群在同种异体BMC植入中发挥明显不同的作用，其中宿主L-和U-NK细胞分别排斥或促进供体同种异体BMC植入。
Natural killer (NK) cells exist as subsets based on expression of inhibitory receptors that recognize major histocompatibility complex I (MHCI) molecules. NK cell subsets bearing MHCI binding receptors for self-MHCI have been termed as "licensed" and exhibit a higher ability to respond to stimuli. In the context of bone marrow transplantation (BMT), host licensed-NK (L-NK) cells have also been demonstrated to be responsible for the acute rejection of allogeneic and MHCI-deficient BM cells (BMCs) in mice after lethal irradiation. However, the role of recipient unlicensed-NK (U-NK) cells has not been well established with regard to allogeneic BMC resistance. After NK cell stimulation, the prior depletion of host L-NK cells resulted in a marked increase of donor engraftment compared with the untreated group. Surprisingly, this increased donor engraftment was reduced after total host NK cell depletion, indicating that U-NK cells can actually promote donor allogeneic BMC engraftment. Furthermore, direct coculture of U-NK cells with allogeneic but not syngeneic BMCs resulted in increased colony-forming unit cell growth in vitro, which was at least partially mediated by granulocyte macrophage colony-stimulating factor (GM-CSF) production. These data demonstrate that host NK cell subsets exert markedly different roles in allogeneic BMC engraftment where host L-and U-NK cells reject or promote donor allogeneic BMC engraftment, respectively.