Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
PLoS One. 2010 Oct 12;5(10):e13294. doi: 10.1371/journal.pone.0013294.
Despite an increasing awareness of the importance of innate immunity, the roles of natural killer (NK) cells in transplant rejection and antiviral and cancer immunity during immunosuppression have not been clearly defined.
To address this issue we have developed a quantitative assay of NK cell function that can be used on clinical samples and have studied the influence of immunosuppression on NK cell function. NK cell degranulation and intracellular interferon (IFN)-γ production were determined by flow cytometry of peripheral blood samples.
Overnight ex vivo treatment of peripheral blood cells from healthy controls with ciclosporin or tacrolimus inhibited NK cell degranulation and IFN-γ production in a dose-dependent manner. A similar impairment of function was seen in NK cells from patients treated in vivo with calcineurin inhibitors. In the early post-transplant period, there was a variable reduction of NK cell counts after treatment with alemtuzumab and basiliximab.
The functional inhibition of NK cells in early transplant patients coincides with the period of maximum susceptibility to viral infections. The ability to assay NK cell function in clinical samples allows assessment of the impact of immunosuppression on these effector cells. This information may be helpful in guiding the titration of immunosuppression in the clinical setting.
尽管人们越来越意识到先天免疫的重要性，但自然杀伤 (NK) 细胞在移植排斥、抗病毒和癌症免疫中的作用在免疫抑制期间仍未得到明确界定。
为了解决这个问题，我们开发了一种定量检测 NK 细胞功能的方法，可用于临床样本，并研究了免疫抑制对 NK 细胞功能的影响。通过外周血样本的流式细胞术测定 NK 细胞脱颗粒和细胞内干扰素 (IFN)-γ 的产生。
环孢素或他克莫司对健康对照者外周血细胞进行 overnight ex vivo 处理，以剂量依赖性方式抑制 NK 细胞脱颗粒和 IFN-γ 的产生。在体内接受钙调神经磷酸酶抑制剂治疗的患者的 NK 细胞中也观察到类似的功能障碍。在移植后的早期，在用阿仑单抗和巴利昔单抗治疗后，NK 细胞计数会出现不同程度的减少。
在早期移植患者中，NK 细胞的功能抑制与对病毒感染的最大易感性时期相吻合。能够在临床样本中检测 NK 细胞功能的能力可用于评估免疫抑制对这些效应细胞的影响。这些信息可能有助于在临床环境中指导免疫抑制的滴定。
