NK-cell education is shaped by donor HLA genotype after unrelated allogeneic hematopoietic stem cell transplantation.
The rules governing natural killer (NK)-cell education in the allogeneic environment created by unrelated hematopoietic stem-cell transplantation (HSCT) are still largely elusive, especially in an unrelated donor setting. NK-cell inhibitory receptors for self-human leukocyte antigen (HLA) play a central role in the acquisition or maintenance of NK-cell functional competence. Therefore, the responsiveness of different NK-cell subsets was assessed as a function of their expression or absence of expression of self-HLA-specific inhibitory receptors, in a large cohort (n = 60) of unrelated HSCT recipients. A fully effective NK-cell education process was achieved within the first year after allogeneic HSCT and lasted for at least 3 years thereafter. In addition, HLA-mismatched HSCT led to a stable education pattern that was determined by the donor's HLA ligands. These data suggest that the NK cell's education partner could be of hematopoietic rather than extrahematopoietic origin. This donor-ligand-driven NK-cell education model would suggest a sustained graft-versus-leukemia effect after HLA-mismatched HSCT.
Inserm, Paris, France.
Philippe
P
Haas
Pascale
P
Loiseau
Ryad
R
Tamouza
Jean-Michel
JM
Cayuela
Hélène
H
Moins-Teisserenc
Marc
M
Busson
Guylaine
G
Henry
Christine S
CS
Falk
Dominique
D
Charron
Gérard
G
Socié
Antoine
A
Toubert
Nicolas
N
Dulphy
D000293:Adolescent; D000328:Adult; D000368:Aged; D001782:Blood Donors; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology / Q000378:metabolism; D054344:Receptors, KIR2DL3 / Q000276:immunology / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous; D055815:Young Adult
D006680:HLA Antigens; D008024:Ligands; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell