Asymptomatic CMV infections in long‐term renal transplant recipients are associated with the loss of FcRγ from LIR‐1+ NK cells |
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Authors: | Nandini B Makwana Bree Foley Silvia Lee Sonia Fernandez Ashley B Irish Patricia Price |
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Institution: | 1. Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia;2. Biomedical Science, Curtin University, Bentley, Australia;3. Telethon Kids Institute, University of Western Australia, Subiaco, Australia;4. Microbiology, Royal Perth Hospital, Perth, Australia;5. Nephrology and Renal Transplantation, Fiona Stanley Hospital, Murdoch, Australia;6. CHIRI, Curtin University, Bentley, Australia |
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Abstract: | While it is established that cytomegalovirus (CMV) disease affects NK‐cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age‐matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR‐1, NKp30, NKp46, and FcRγ, a signaling adaptor molecule, on CD56dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK‐cell function as assessed by TNF‐α and CD107a expression. The most active NK cells were FcRγ–LIR‐1+NKG2C– and displayed high antibody‐dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom‐free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcRγ but express LIR‐1. |
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Keywords: | CMV Cytokines Cytotoxicity Natural killer cells Renal transplantation |
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