title: Amplified NKG2C+ NK cells in cytomegalovirus (CMV) infection preferentially express killer cell Ig-like receptor 2DL: functional impact in controlling CMV-infected dendritic cells.
abstract: CMV infection represents a major complication in hematopoietic stem cell transplantation, which compromises graft outcome. Downregulation of HLA class I expression is one mechanism by which CMV evades T cell-mediated immune detection, rendering infected cells vulnerable to killer cell Ig-like receptor (KIR)(+) NK cells. In this study, we observed that the amplified NKG2C(+) NK cell population observed specifically in CMV seropositive individuals mainly expressed KIR2DL receptors. We have shown that HLA class I expression was downregulated on CMV-infected immature dendritic cells (iDCs), which escape to HLA-A2-pp65-specific T lymphocytes but strongly trigger the degranulation of KIR2D(+) NK cells. CMV infection conferred a vulnerability of C2C2(+) iDCs to educated KIR2DL1(+) and KIR2DL3(+) NK cell subsets. Alloreactivity of KIR2DL1(+) NK cell subsets against C1C1(+) iDCs was maintained independently of CMV infection. Unexpectedly, CMV-infected C1C1(+) iDCs did not activate KIR2DL3(+) NK cell reactivity, suggesting a potential CMV evasion to KIR2DL3 NK cell recognition. Altogether, the coexpression of KIR and NKG2C on expanded NK cell subsets could be related to a functional contribution of KIR in CMV infection and should be investigated in hematopoietic stem cell transplantation, in which the beneficial impact of CMV infection has been reported on the graft-versus-leukemia effect.
authors.affiliation: Etablissement Français du Sang-Pays de la Loire, EA4271, Immunovirologie et Polymorphisme Génétique, 44011 Nantes Cedex 01, France.
authors.forename: Zakia
authors.initials: Z
authors.lastname: Djaoud
authors.forename: Gaëlle
authors.initials: G
authors.lastname: David
authors.forename: Céline
authors.initials: C
authors.lastname: Bressollette
authors.forename: Catherine
authors.initials: C
authors.lastname: Willem
authors.forename: Pauline
authors.initials: P
authors.lastname: Rettman
authors.forename: Katia
authors.initials: K
authors.lastname: Gagne
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Legrand
authors.forename: Souad
authors.initials: S
authors.lastname: Mehlal
authors.forename: Anne
authors.initials: A
authors.lastname: Cesbron
authors.forename: Berthe-Marie
authors.initials: BM
authors.lastname: Imbert-Marcille
authors.forename: Christelle
authors.initials: C
authors.lastname: Retière
mesh_terms: D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology* / Q000378:metabolism; D054340:Receptors, KIR / Q000096:biosynthesis* / Q000276:immunology; D054342:Receptors, KIR2DL1 / Q000096:biosynthesis / Q000276:immunology; D054344:Receptors, KIR2DL3 / Q000096:biosynthesis / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; C093100:KIR2DL1 protein, human; C515078:KIR2DL3 protein, human; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3