Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants.
T cells that accompany allogeneic hematopoietic grafts for treating leukemia enhance engraftment and mediate the graft-versus-leukemia effect. Unfortunately, alloreactive T cells also cause graft-versus-host disease (GVHD). T cell depletion prevents GVHD but increases the risk of graft rejection and leukemic relapse. In human transplants, we show that donor-versus-recipient natural killer (NK)-cell alloreactivity could eliminate leukemia relapse and graft rejection and protect patients against GVHD. In mice, the pretransplant infusion of alloreactive NK cells obviated the need for high-intensity conditioning and reduced GVHD. NK cell alloreactivity may thus provide a powerful tool for enhancing the efficacy and safety of allogeneic hematopoietic transplantation.
Ruggeri
Loredana
L
Department of Clinical and Experimental Medicine, Section of Hematology and Clinical Immunology, Perugia University School of Medicine, Perugia, Italy.
Capanni
Marusca
M
Urbani
Elena
E
Perruccio
Katia
K
Shlomchik
Warren D
WD
Tosti
Antonella
A
Posati
Sabrina
S
Rogaia
Daniela
D
Frassoni
Francesco
F
Aversa
Franco
F
Martelli
Massimo F
MF
Velardi
Andrea
A
D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D018572:Disease-Free Survival; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D020544:Graft vs Leukemia Effect; D006183:H-2 Antigens / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D011971:Receptors, Immunologic / Q000378:metabolism; D054340:Receptors, KIR; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning
D006183:H-2 Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR