title: Alloreactive natural killer cells in mismatched hematopoietic stem cell transplantation.
abstract: Natural killer (NK) cell-mediated, donor-vs.-recipient alloresponses occur following transplantation of human leukocyte antigen (HLA) haplotype-mismatched hematopoietic stem cells (HSCs). NK cell alloreactivity reduced the risk of relapse in acute myeloid leukemia patients while improving engraftment and protecting against graft-vs.-host disease (GvHD). NK cells are primed to kill by several activating receptors. NK killing of autologous cells is prevented because NK cells co-express inhibitory receptors (killer cell Ig-like receptors, KIR) that recognize groups of (self) MHC class I alleles. As KIRs are clonally distributed, the NK population in any individual is constituted of a repertoire with different allospecificities. NK cells in the repertoire mediate alloreactions when the allogeneic targets do not express class I alleles that block them. High resolution molecular HLA typing of recipient and donor, positive identification of donor KIR genes, and in some cases, functional assessment of donor NK clones will identify haploidentical donors who are able to mount donor-vs.-recipient NK alloreactions.
authors.affiliation: Department of Clinical and Experimental Medicine, Haematology and Clinical Immunology, University of Perugia, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Marusca
authors.initials: M
authors.lastname: Capanni
authors.forename: Antonella
authors.initials: A
authors.lastname: Mancusi
authors.forename: Elena
authors.initials: E
authors.lastname: Urbani
authors.forename: Katia
authors.initials: K
authors.lastname: Perruccio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Burchielli
authors.forename: Antonella
authors.initials: A
authors.lastname: Tosti
authors.forename: Fabiana
authors.initials: F
authors.lastname: Topini
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
mesh_terms: D000818:Animals; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006650:Histocompatibility Testing; D006789:Host vs Graft Reaction / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I