title: KIR2DS1-dependent acquisition of CCR7 and migratory properties by human NK cells interacting with allogeneic HLA-C2+ DCs or T-cell blasts.
abstract: Natural killer (NK) cells may capture the CCR7 chemokine receptor from allogeneic CCR7(+) cells by trogocytosis and acquire migrating properties in response to lymph node chemokines. This event is negatively regulated by inhibitory killer Ig-like receptors (KIRs) and NKG2A. In this study, we analyzed the role of the HLA-C2-specific activating receptor KIR2DS1 in the process of CCR7 uptake by NK cells interacting with different allogeneic CCR7(+) cells. Co-incubation of KIR2DS1(+) fresh NK cells or NK-cell clones with HLA-C2(+) CCR7(+) lymphoblastoid cell lines resulted in increased CCR7 uptake. Remarkably, KIR2DS1 expression represented a major advantage for acquiring CCR7 from HLA-C2(+) allogeneic dendritic cells (DCs) and T-cell blasts. These findings have important implications in haploidentical hematopoietic stem cell transplantation in which donor-derived (alloreactive) KIR2DS1(+) NK cells, upon CCR7 acquisition, become capable of migrating toward lymph nodes, where they may kill patient DCs and T cells, preventing graft-versus-host and host-versus-graft reactions.
authors: Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genoa, Italy.
authors: Emanuela
authors: E
authors: Marcenaro
authors: Silvia
authors: S
authors: Pesce
authors: Simona
authors: S
authors: Sivori
authors: Simona
authors: S
authors: Carlomagno
authors: Lorenzo
authors: L
authors: Moretta
authors: Alessandro
authors: A
authors: Moretta
mesh_terms: D001752:Blast Crisis / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement; D002633:Chemotaxis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015236:HLA-C Antigens / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism*; D054340:Receptors, KIR / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: C515370:CCR7 protein, human; D015236:HLA-C Antigens; C496212:KIR2DS1 protein, human; D054400:Receptors, CCR7; D054340:Receptors, KIR