renal transplant immunosuppression impairs natural killer cell function in vitro and in vivo肾移植免疫抑制损害自然杀伤细胞功能在体外和体内.pdfVIP

Renal Transplant Immunosuppression Impairs Natural Killer Cell Function In Vitro and In Vivo 1 1 1,2 1 1 Olivier Morteau , Samkeliso Blundell , Aron Chakera , Sophia Bennett , Charita M. Christou , Philip D. 2 1,2 . 1,2 . Mason , Richard J. Cornall * , Christopher A. O’Callaghan * 1 Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom, 2 Oxford Kidney Unit, Churchill Hospital, Oxford, United Kingdom Abstract Background: 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. Methods: 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)-c production were determined by flow cytometry of peripheral blood samples. Results: Overnight ex vivo treatment of peripheral blood cells from healthy controls with ciclosporin or tacrolimus inhibited NK cell degranulation and IFN-c 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. Conclusions: The functional inhibition of NK cells in early transplant patients coincides with the period of maximum susceptibility to viral i