title: Modulation of the natural killer cell KIR repertoire by cytomegalovirus infection.
abstract: Patients carrying activating killer cell immunoglobulin-like receptor (KIR) genes are significantly protected from CMV-associated complications after solid organ or hematopoietic stem cell transplantation. Whether previous infection with CMV affects NK-cell function in healthy donors is unknown. We studied the KIR repertoire and alterations of KIR expression after in vitro exposure to CMV in 54 healthy donors. The expression of neither activating nor inhibitory KIRs was different at baseline between 23 seropositive and 31 seronegative donors. However, after co-culture of NK cells with CMV-infected fibroblast cells, expression of the inhibitory receptors KIR2DL1 and KIR2DL3 and the activating receptor KIR3DS1 significantly increased in CMV-seropositive donors. In CMV-seronegative donors, changes were subtle and restricted to the subset of NK cells expressing NK-cell group antigen 2C (NKG2C). Expansion of inhibitory KIRs occurred exclusively in donors carrying the cognate HLA class I ligands, whereas the presence of the putative ligand HLA-Bw4 was not necessary for the expansion of KIR3DS1-expressing NK cells. Our data show that previous infection with CMV does not alter the resting NK-cell receptor repertoire, but appears to modify how NK cells respond to re-exposure to CMV in vitro.
authors.affiliation: Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Hojjatollah N
authors.initials: HN
authors.lastname: Charoudeh
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Terszowski
authors.forename: Karol
authors.initials: K
authors.lastname: Czaja
authors.forename: Asensio
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Karin
authors.initials: K
authors.lastname: Schmitter
authors.forename: Martin
authors.initials: M
authors.lastname: Stern
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D018920:Coculture Techniques / Q000379:methods; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005805:Genes, MHC Class I / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008024:Ligands; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology / Q000378:metabolism; D054340:Receptors, KIR / Q000276:immunology* / Q000378:metabolism; D054342:Receptors, KIR2DL1 / Q000276:immunology / Q000378:metabolism; D054344:Receptors, KIR2DL3 / Q000276:immunology / Q000378:metabolism; D054349:Receptors, KIR3DS1 / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C093100:KIR2DL1 protein, human; C515078:KIR2DL3 protein, human; C527059:KLRC2 protein, human; D008024:Ligands; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D054349:Receptors, KIR3DS1