title: Expression of killer cell immunoglobulin-like receptors (KIRs) by natural killer cells during acute CMV infection after kidney transplantation.
abstract: Human cytomegalovirus (CMV) infection may be a serious complication related to immunosuppression after solid organ transplantation. Due to their cytotoxicity, T-cells and natural killer (NK) cells target and clear the virus from CMV-infected cells. Although immunosuppressive drugs suppress T-cell proliferation and activation, they do not affect NK cells that are crucial for controlling the infection. The regulation of NK cells depends on a wide range of activating and inhibitory receptors such as the family of killer-cell immunoglobulin-like receptors (KIRs). Several human genetic studies have demonstrated the association of KIR genes with the clearance of infections. Since the respective activities of the different KIR proteins expressed by NK cells during CMV infection have not been extensively studied, we analyzed the expression of KIRs in a cohort of 22 CMV-IgG(+) renal transplant patients at the time of CMV reactivation, after antiviral therapy and 6 months later. Our data revealed a marked expression of KIR3DL1 during the acute phase of the reactivation. We set up an in vitro model in which NK cells, derived either from healthy donors or from transplanted patients, target allogeneic fibroblasts, CMV-infected or uninfected. Our results demonstrate a significant correlation between the lysis of CMV-infected fibroblasts and the expression of KIR3DL1. Blocking experiments with antibodies to MHC-I, to NKG2D and to NKG2C confirmed the importance of KIR3DL1. Consequently, our results suggest that KIR proteins and especially KIR3DL1 could play an important role during CMV-infection or CMV reactivation in immunosuppressed patients.
authors.affiliation: Transplant Immunology Unit, Division of Immunology and Allergy, University Hospital Geneva, Switzerland; Division of Laboratory Medicine, University Hospital Geneva, Switzerland.
authors.forename: Casimir
authors.initials: C
authors.lastname: de Rham
authors.affiliation: Division of Nephrology, Department of Medicine Specialties, University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Karine
authors.initials: K
authors.lastname: Hadaya
authors.affiliation: Service of Internal Medicine, CHUV, Lausanne, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Bandelier
authors.affiliation: Transplant Immunology Unit, Division of Immunology and Allergy, University Hospital Geneva, Switzerland; Division of Laboratory Medicine, University Hospital Geneva, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ferrari-Lacraz
authors.affiliation: Transplant Immunology Unit, Division of Immunology and Allergy, University Hospital Geneva, Switzerland. Electronic address: Jean.villard@hcuge.ch.
authors.forename: Jean
authors.initials: J
authors.lastname: Villard
mesh_terms: D000208:Acute Disease; D019138:Antibodies, Blocking / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D011183:Postoperative Complications / Q000276:immunology*; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014775:Virus Activation / Q000187:drug effects / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1
keywords: Allogeneic fibroblast; Cytomegalovirus; KIR; NK cell