Renal transplant immunosuppression impairs natural killer cell function in vitro and in vivo.
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)-γ 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-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.


CONCLUSIONS
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.
Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Olivier
O
Morteau
Samkeliso
S
Blundell
Aron
A
Chakera
Sophia
S
Bennett
Charita M
CM
Christou
Philip D
PD
Mason
Richard J
RJ
Cornall
Christopher A
CA
O'Callaghan
D015550:Cell Degranulation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D016572:Cyclosporine; D016559:Tacrolimus