Adaptive NK cell reconstitution is associated with better clinical outcomes
Adaptive NK cell reconstitution is associated with better clinical outcomes
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DOI：
10.1172/jci.insight.125553
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发表时间：
2019-01-24
期刊：
影响因子：
8
通讯作者：
Miller, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Cichocki, Frank;Tams, Emily;Miller, Jeffrey S.
背景人巨细胞病毒（CMV）再激活是移植后早期常见的现象，与异源NK细胞亚群扩增有关。这些适应性NK细胞扩增在接受者之间是高度可变的，关于适应性NK细胞亚群的幅度和相对频率。为了深入了解影响CMV幼稚移植物来源的适应性NK细胞扩增的因素，我们对215例移植了2个部分HLA匹配的CMV阴性脐带血单位的血液恶性肿瘤患者进行了高分辨率NK细胞和CD 8（+）T细胞表型分析。我们发现，适应性NK细胞显着较高的收件人接受非清髓性条件（NMAC）相对于清髓性条件（MAC），高CMV中和抗体滴度与适应性NK细胞扩增的程度。从供体造血祖细胞重建的适应性NK细胞亚群（定义为NKG 2C、Fc受体γ、EAT-2和SYK表达）的频率在很大程度上与预处理前受体NK细胞区室中观察到的频率相匹配，表明宿主-以及病毒再活化因子-可能决定移植后的表型多样化。此外，多变量分析显示，较高的适应性NK细胞扩增与较好的无病生存率相关。我们的研究结果为移植后适应性NK细胞重建提供了重要的见解，并支持适应性NK细胞在促进更好的临床结局中的作用。NIH和国家骨髓捐献者计划。
BACKGROUND. Human cytomegalovirus (CMV) reactivation is a common occurrence early after transplant and is associated with heterogeneous NK cell subset expansion. These adaptive NK cell expansions are highly variable between recipients, with respect to magnitude and relative frequencies of adaptive NK cell subsets.METHODS. To gain insight into the factors that influence adaptive NK cell expansion from a CMV naive graft source, we performed a high-resolution NK cell and CD8(+) T cell phenotypic analysis of 215 patients with hematological malignancies that were transplanted with 2 partially HLA matched CMV negative umbilical cord blood units.RESULTS. We found that adaptive NK cells were significantly higher in recipients who received nonmyeloablative conditioning (NMAC) relative to myeloablative conditioning (MAC), and high CMV neutralizing antibody titers correlated with the degree of adaptive NK cell expansion. The frequencies of adaptive NK cell subsets (defined by NKG2C, Fc epsilon R gamma, EAT-2, and SYK expression) that reconstitute from donor hematopoietic progenitor cells largely matched the frequencies observed in the NK cell compartment of the recipient prior to conditioning, suggesting that host - as well as viral reactivation factors - may determine the phenotypic diversification after transplant. Additionally, multivariable analyses show that higher adaptive NK cell expansion associated with better disease-free survival.CONCLUSIONS. Our findings provide important insights into adaptive NK cell reconstitution after transplant and support a role for adaptive NK cells in promoting better clinical outcomes.FUNDING. The NIH and the National Marrow Donor Program.