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

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)-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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1371/journal.pone.0013294

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Institution:
University of Oxford
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Institution:
University of Oxford
Role:
Author
More by this author
Institution:
University of Oxford
Role:
Author
More by this author
Institution:
University of Oxford
Role:
Author
More by this author
Institution:
University of Oxford
Role:
Author


Publisher:
Public Library of Science
Journal:
PloS one More from this journal
Volume:
5
Issue:
10
Article number:
e13294
Publication date:
2010-01-01
DOI:
EISSN:
1932-6203
ISSN:
1932-6203


Language:
English
Keywords:
Pubs id:
90805
UUID:
uuid:e927ce61-93dc-47fa-a2b3-261dfd89b673
Local pid:
pubs:90805
Source identifiers:
90805
Deposit date:
2012-12-19
ARK identifier:

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