Alloreactive natural killer cells in mismatched hematopoietic stem cell transplantation.
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.
Ruggeri
Loredana
L
Department of Clinical and Experimental Medicine, Haematology and Clinical Immunology, University of Perugia, Italy.
Capanni
Marusca
M
Mancusi
Antonella
A
Urbani
Elena
E
Perruccio
Katia
K
Burchielli
Emanuela
E
Tosti
Antonella
A
Topini
Fabiana
F
Aversa
Franco
F
Martelli
Massimo F
MF
Velardi
Andrea
A
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
D015395:Histocompatibility Antigens Class I