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 a...

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Main Authors: Morteau, O., Blundell, S., Chakera, Aron, Bennett, S., Christou, C., Mason, P., Cornall, R., O'Callaghan, C.
Format: Journal Article
Published: Public Library of Science 2010
Online Access:http://hdl.handle.net/20.500.11937/24555
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author Morteau, O.
Blundell, S.
Chakera, Aron
Bennett, S.
Christou, C.
Mason, P.
Cornall, R.
O'Callaghan, C.
author_facet Morteau, O.
Blundell, S.
Chakera, Aron
Bennett, S.
Christou, C.
Mason, P.
Cornall, R.
O'Callaghan, C.
author_sort Morteau, O.
building Curtin Institutional Repository
collection Online Access
description 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)-? 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-? 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. © 2010 Morteau et al.
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spelling curtin-20.500.11937-245552017-09-13T15:10:08Z Renal transplant immunosuppression impairs natural killer cell function in Vitro and in vivo Morteau, O. Blundell, S. Chakera, Aron Bennett, S. Christou, C. Mason, P. Cornall, R. O'Callaghan, C. 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)-? 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-? 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. © 2010 Morteau et al. 2010 Journal Article http://hdl.handle.net/20.500.11937/24555 10.1371/journal.pone.0013294 Public Library of Science unknown
spellingShingle Morteau, O.
Blundell, S.
Chakera, Aron
Bennett, S.
Christou, C.
Mason, P.
Cornall, R.
O'Callaghan, C.
Renal transplant immunosuppression impairs natural killer cell function in Vitro and in vivo
title Renal transplant immunosuppression impairs natural killer cell function in Vitro and in vivo
title_full Renal transplant immunosuppression impairs natural killer cell function in Vitro and in vivo
title_fullStr Renal transplant immunosuppression impairs natural killer cell function in Vitro and in vivo
title_full_unstemmed Renal transplant immunosuppression impairs natural killer cell function in Vitro and in vivo
title_short Renal transplant immunosuppression impairs natural killer cell function in Vitro and in vivo
title_sort renal transplant immunosuppression impairs natural killer cell function in vitro and in vivo
url http://hdl.handle.net/20.500.11937/24555