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.