Natural killer cells as a therapeutic tool in mismatched transplantation.
Natural-killer-cell-mediated, donor-vs-recipient alloresponses occur following transplantation of human-leukocyte-antigen (HLA)-haplotype-mismatched haematopoietic stem cells. Natural killer (NK) cell alloreactivity reduces the risk of relapse in acute myeloid leukaemia patients, while improving engraftment and protecting against graft-vs-host disease. NK cells are primed to kill by several activating receptors. NK cell killing of autologous cells is prevented as NK cells co-express inhibitory receptors (killer cell Ig-like receptors, KIR) that recognize groups of (self) major histocompatibility complex class I alleles. As KIRs are distributed clonally, the NK cell population in any individual constitutes 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 haplo-identical donors who are able to mount donor-vs-recipient NK alloreactions.
Ruggeri
Loredana
L
Division of Haematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Policlinico Monteluce, Via Brunamonti 06100, Perugia, Italy.
Capanni
Marusca
M
Mancusi
Antonella
A
Aversa
Franco
F
Martelli
Massimo F
MF
Velardi
Andrea
A
D019264:Adoptive Transfer / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007694:Killer Cells, Natural / Q000637:transplantation*; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D014181:Transplantation Immunology / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology