title: Uptake of CCR7 and acquisition of migratory properties by human KIR+ NK cells interacting with monocyte-derived DC or EBV cell lines: regulation by KIR/HLA-class I interaction.
abstract: C-C chemokine receptor type 7 (CCR7) is a chemokine receptor playing a pivotal role in the induction of human natural killer (NK)-cell migration to lymph nodes. We show that "licensed" peripheral blood killer immunoglobulin-like receptor-positive (KIR(+)) NK-cell populations, as well as KIR(+) NK-cell clones, de novo express CCR7 upon coculture with mature dendritic cells (mDCs) or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines. As a consequence, they become capable of migrating in response to the CCR7-specific chemokines C-C chemokine ligand (CCL)-19 and/or CCL21. The acquisition of CCR7 by NK cells requires direct cell-to-cell contact, is detectable within a few minutes, and is due to receptor uptake from CCR7(+) cells. This mechanism is tightly regulated by KIR-mediated recognition of human leukocyte antigen (HLA) class I as well as by adhesion molecules including leukocyte function-associated antigen 1 (LFA-1) and CD2. Analysis of NK-cell clones revealed that alloreactive (KIR-ligand mismatched) but not autologous NK cells acquire CCR7. These data have important implications in haploidentical hematopoietic stem cell transplantation (HSCT), in which alloreactive NK cells may acquire the ability to migrate to secondary lymphoid compartments (SLCs), where they can kill recipient antigen-presenting cells (APCs) and T cells thus preventing graft-versus-host (and host-versus-graft) reactions.
authors.affiliation: Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genova, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Silvia
authors.initials: S
authors.lastname: Pesce
authors.forename: Carola
authors.initials: C
authors.lastname: Prato
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.forename: Sophie
authors.initials: S
authors.lastname: Agaugué
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
mesh_terms: D001324:Autoantigens / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement; D002472:Cell Transformation, Viral; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D006087:Graft vs Host Reaction / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006789:Host vs Graft Reaction / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology / Q000821:virology; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D054400:Receptors, CCR7 / Q000378:metabolism*; D054340:Receptors, KIR / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C515370:CCR7 protein, human; D018801:CD2 Antigens; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D016169:Lymphocyte Function-Associated Antigen-1; D054400:Receptors, CCR7; D054340:Receptors, KIR