Abstract
BackgroundDespite 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.MethodsTo 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.ResultsOvernight 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.ConclusionsThe 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.
Highlights
Natural killer (NK) cells have potent effector functions and play a key role in a range of immune responses, including those against pathogens and cancers [1]; their role in transplantation and response to transplant immunosuppression are not clearly defined
The inhibitory receptors include the CD94/NKG2A/B heterodimers, which we identified as receptors for human leukocyte antigen (HLA)-E, and killer inhibitory receptors (KIR) which interact with major histocompatibility complex (MHC) class I molecules [3,4,5]
Refinement and validation of an assay of natural killer (NK) cell function To measure NK cell function ex vivo, we first developed an assay of cytotoxic degranulation and cytokine production that was sensitive and reproducible using peripheral blood samples
Summary
Natural killer (NK) cells have potent effector functions and play a key role in a range of immune responses, including those against pathogens and cancers [1]; their role in transplantation and response to transplant immunosuppression are not clearly defined. NK cells have two key effector functions, which are the cytotoxic lysis of target cells and the release of inflammatory cytokines that amplify the immune response, including interferon (IFN)-c [1]. 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
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