Innate immunity against hematological malignancies.
BACKGROUND
Allogeneic hematopoietic transplantation relies on T-cell alloreactions for engraftment and the GvL effect. In HLA haplotype-mismatched transplants, extensive T-cell depletion of the graft is essential to prevent GvHD. This raises the question of whether mismatched transplants exert any GvL effect, and whether it will ever be possible to reduce the intensity of preparative regimens. Natural killer (NK) cells are negatively regulated by MHC Class I-specific inhibitory receptors. Mismatched transplants may therefore trigger NK-cell alloreactivity.


METHODS
The effects of NK-cell alloreactivity were evaluated in clinical transplantation and in murine transplant models.


RESULTS
In clinical hematopoietic stem-cell transplants, HLA Class I disparities driving NK-cell alloreactions in the GvH direction eliminate AML relapse and graft rejection, while protecting patients from GvHD. In murine MHC mismatched transplant models, the pre-transplant infusion of donor-versus-recipient alloreactive NK cells conditioned the recipients to BMT, and reduced GvHD.


CONCLUSIONS
NK-cell alloreactivity may thus provide a novel, powerful tool for enhancing the efficacy and safety of allogeneic hematopoietic transplantation.
Ruggeri
L
L
Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Capanni
M
M
Tosti
A
A
Urbani
E
E
Posati
S
S
Aversa
F
F
Martelli
M F
MF
Velardi
A
A
D000818:Animals; D004195:Disease Models, Animal; D005805:Genes, MHC Class I; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
D006680:HLA Antigens