Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro

Tschan-Plessl, A. and Stern, M. and Schmied, L. and Retiere, C. and Hirsch, H. H. and Garzoni, C. and van Delden, C. and Boggian, K. and Mueller, N. J. and Berger, C. and Villard, J. and Manuel, O. and Meylan, P. and Terszowski, G.. (2016) Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro. Transplant Direct, 2 (7). e89.

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Official URL: https://edoc.unibas.ch/61876/

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BACKGROUND: Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive. METHODS: We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant. Seronegative recipients of seronegative kidney grafts served as controls. RESULTS: We observed a significant increase of NKG2C expressing NK cells after CMV infection (mean increase, 17.5%; 95% confidence interval [95% CI], 10.2-24.9, P > 0.001), whereas cluster of differentiation (CD)57 expressing cells decreased (mean decrease, 14.1%; 95% CI, 8.0-20.2; P > 0.001). Analysis of killer immunoglobulin-like receptor (KIR) expression showed an increase of cells expressing KIR2DL1 as their only inhibitory KIR in patients carrying the cognate ligand HLA-C2 (mean increase, 10.0%; 95% CI, 1.7-18.3; P = 0.018). In C2-negative individuals, KIR2DL1 expression decreased (mean decrease, 3.9%; 95% CI, 1.6-6.2; P = 0.001). As for activating KIR, there was no conclusive change pattern. Most importantly, we observed a significantly higher NK cell degranulation and IFNgamma production in response to different target cells (target K562, CD107a: mean increase, 9.9%; 95% CI, 4.8-15.0; P > 0.001; IFNgamma: mean increase, 6.6%; 95% CI, 1.6-11.1; P > 0.001; target MRC-5, CD107a: mean increase, 6.9%; 95% CI, 0.7-13.1; P = 0.03; IFNgamma: mean increase, 4.8%; 95% CI, 1.7-7.8; P = 0.002). CONCLUSIONS: We report evidence for an increased function of NK cells induced by CMV infection. This increased in vitro functionality was seen in NKG2C-positive and NKG2C-negative subsets, arguing for an NKG2C independent mechanism of action.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Transplantation Virology (Hirsch)
UniBasel Contributors:Hirsch, Hans H.
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2373-8731 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 May 2020 21:23
Deposited On:31 May 2020 21:23

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