title: Bridging innate NK cell functions with adaptive immunity.
abstract: Killer Ig-like receptors (KIRs) are major human NK receptors displaying either inhibitory or activating functions which recognize allotypic determinants of HLA-class I molecules. Surprisingly, NK cell treatment with CpG-ODN (TLR9 ligands) results in selective down-modulation of KIR3DL2, its co-internalization with CpG-ODN and its translocation to TLR9-rich early endosomes. This novel KIR-associated function may offer clues to better understand the possible role of certain KIRs and also emphasizes the involvement of NK cells in the course of microbial infections. NK cells are involved not only in innate immune responses against viruses and tumors but also participate in the complex network of cell-to cell interaction that leads to the development of adaptive immune responses. In this context the interaction of NK cells with DC appears to play a crucial role in the acquisition of CCR7, a chemokine receptor that enables NK cells to migrate towards lymph nodes in response to CCL19 and/or CCL21. Analysis of NK cell clones revealed that KIR-mismatched but not KIR-matched NK cells acquire CCR7. These data have important implications in haploidentical haematopoietic stem cell transplantation (HSCT), in which KIR-mismatched NK cells may acquire the ability to migrate to secondary lymphoid compartments (SLCs), where they can kill recipient's antigen presenting cells (APCs) and T cells thus preventing graft versus host (and host vs. graft) reactions.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.forename: Simona
authors.initials: S
authors.lastname: Carlomagno
authors.forename: Silvia
authors.initials: S
authors.lastname: Pesce
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Simona
authors.initials: S
authors.lastname: Sivori
mesh_terms: D056704:Adaptive Immunity; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D054415:Chemokine CCL19 / Q000276:immunology / Q000378:metabolism; D054421:Chemokine CCL21 / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D054400:Receptors, CCR7 / Q000276:immunology / Q000378:metabolism; D054340:Receptors, KIR / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism; D014185:Transplantation, Isogeneic
chemical_list: C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C408982:CPG-oligonucleotide; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D015395:Histocompatibility Antigens Class I; D009838:Oligodeoxyribonucleotides; D054400:Receptors, CCR7; D054340:Receptors, KIR; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9