title: Asymptomatic CMV infections in long-term renal transplant recipients are associated with the loss of FcRγ from LIR-1+NK cells.
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 CD56dimNK 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.
authors: Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia.|Biomedical Science, Curtin University, Bentley, Australia.
authors: Nandini B
authors: NB
authors: Makwana
authors: Telethon Kids Institute, University of Western Australia, Subiaco, Australia.
authors: Bree
authors: B
authors: Foley
authors: Biomedical Science, Curtin University, Bentley, Australia.|Microbiology, Royal Perth Hospital, Perth, Australia.
authors: Silvia
authors: S
authors: Lee
authors: Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia.
authors: Sonia
authors: S
authors: Fernandez
authors: Nephrology and Renal Transplantation, Fiona Stanley Hospital, Murdoch, Australia.
authors: Ashley B
authors: AB
authors: Irish
authors: Biomedical Science, Curtin University, Bentley, Australia. patricia.price@curtin.edu.au.|CHIRI, Curtin University, Bentley, Australia. patricia.price@curtin.edu.au.
authors: Patricia
authors: P
authors: Price
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D058345:Asymptomatic Infections; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000235:genetics; D054353:Perforin / Q000032:analysis; D010641:Phenotype; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; C527059:KLRC2 protein, human; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; D054353:Perforin
keywords: CMV; Cytokines; Cytotoxicity; Natural killer cells; Renal transplantation