Natural killer cell alloreactivity in allogeneic hematopoietic transplantation.
OBJECTIVE
This review will focus on the translation of natural killer cell recognition of missing self into the clinical practice of allogeneic hematopoietic transplantation and discuss how it has opened innovative perspectives in the cure of leukemia. Allogeneic hematopoietic stem cell transplantation from a human leukocyte antigen-matched sibling can cure leukemia but 75% of patients do not have a matched donor, one alternative source of stem cells includes full haplotype mismatched family members. As haploidentical transplantation must be extensively T cell depleted to prevent lethal graft-versus-host disease, it cannot rely on donor T cells for the graft-versus-leukemia effect. Mismatched transplantation, however, triggers alloreactivity mediated by natural killer cells which is based upon 'missing self recognition'.


METHODS
Recent studies using preclinical murine models of haploidentical transplantation demonstrated that conditioning with alloreactive natural killer cells ablates the recipient immune system and leukemia cells. In the clinical setting of mismatched hematopoietic stem cell transplantation, donor versus recipient natural killer cell alloreactivity has been associated with better outcome, particularly in patients with acute myeloid leukemia who are transplanted in remission.


CONCLUSIONS
Given the benefits of natural killer cell alloreactivity, it is expected that it will encourage greater use of haploidentical transplants for the large numbers of leukemia patients without matched donors.
Ruggeri
Loredana
L
Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. loredana.ruggeri@unipg.it
Mancusi
Antonella
A
Burchielli
Emanuela
E
Aversa
Franco
F
Martelli
Massimo F
MF
Velardi
Andrea
A
D000818:Animals; D046148:Donor Selection; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000628:therapy*; D051379:Mice; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D006680:HLA Antigens