HLA-E upregulation on IFN-gamma-activated AML blasts impairs CD94/NKG2A-dependent NK cytolysis after haplo-mismatched hematopoietic SCT.
Natural killer (NK) cells generated after haploidentical hematopoietic SCT in patients with AML are characterized by specific phenotypic features and impaired functioning that may affect transplantation outcome. We show that IFN-gamma produced by immature CD56(bright) NK cells upregulates cell surface expression of HLA-E on AML blasts and that this upregulation protects leukemic cells from NK-mediated cell lysis through the mediation of CD94/NKG2A, an inhibitory receptor overexpressed on NK cells after haploidentical SCT. Two years after transplantation, however, maturing NK cells were functionally active, as evidenced by high cytotoxicity and poor IFN-gamma production. This implies that maturation of NK cells is the key to improved immune responses and transplantation outcome.
Nguyen
S
S
Laboratoire d'Immunologie Cellulaire et Tissulaire, Institut National de la Santé et de la Recherche Médicale U543, Hôpital Pitié-Salpêtrière, Paris, France.
Beziat
V
V
Dhedin
N
N
Kuentz
M
M
Vernant
J P
JP
Debre
P
P
Vieillard
V
V
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000473:pathology* / Q000628:therapy; D008297:Male; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology*; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human