Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Center for Virology and Vaccines Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2019 Aug 23;10:1890. doi: 10.3389/fimmu.2019.01890. eCollection 2019.
A previously proposed immune risk profile (IRP), based on T cell phenotype and CMV serotype, is associated with mortality in the elderly and increased infections post-kidney transplant. To evaluate if NK cells contribute to the IRP and if the IRP can be predicted by a clinical T cell functional assays, we conducted a cross sectional study in renal transplant candidates to determine the incidence of IRP and its association with specific NK cell characteristics and ImmuKnow® value. Sixty five subjects were enrolled in 5 cohorts designated by age and dialysis status. We determined T and NK cell phenotypes by flow cytometry and analyzed multiple factors contributing to IRP. We identified 14 IRP+ [CMV seropositivity and CD4/CD8 ratio < 1 or being in the highest quintile of CD8+ senescent (28CD-/CD57+) T cells] individuals equally divided amongst the cohorts. Multivariable linear regression revealed a distinct IRP+ group. Age and dialysis status did not predict immune senescence in kidney transplant candidates. NK cell features alone could discriminate IRP- and IRP+ patients, suggesting that NK cells significantly contribute to the overall immune status in kidney transplant candidates and that a combined T and NK cell phenotyping can provide a more detailed IRP definition. ImmuKnow® value was negatively correlated to age and significantly lower in IRP+ patients and predicts IRP when used alone or in combination with NK cell features. NK cells contribute to overall immune senescence in kidney transplant candidates.
先前提出的免疫风险谱(IRP)基于 T 细胞表型和 CMV 血清型,与老年人的死亡率和肾移植后感染增加有关。为了评估 NK 细胞是否有助于 IRP,以及 IRP 是否可以通过临床 T 细胞功能检测来预测,我们在肾移植候选者中进行了一项横断面研究,以确定 IRP 的发生率及其与特定 NK 细胞特征和 ImmuKnow®值的关系。65 名受试者分为 5 个队列,按年龄和透析状态分组。我们通过流式细胞术确定 T 和 NK 细胞表型,并分析了导致 IRP 的多种因素。我们确定了 14 名 IRP+(CMV 血清阳性和 CD4/CD8 比值<1 或 CD8+衰老(28CD-/CD57+)T 细胞最高五分位数)个体,这些个体在队列中均匀分布。多变量线性回归显示出一个独特的 IRP+组。年龄和透析状态不能预测肾移植候选者的免疫衰老。NK 细胞特征本身可以区分 IRP-和 IRP+患者,这表明 NK 细胞在肾移植候选者的整体免疫状态中具有重要作用,并且 T 和 NK 细胞表型的组合可以提供更详细的 IRP 定义。ImmuKnow®值与年龄呈负相关,在 IRP+患者中显著降低,并且可以单独使用或与 NK 细胞特征结合使用来预测 IRP。NK 细胞有助于肾移植候选者的整体免疫衰老。