HLA-E upregulation on IFN-γ-activated AML blasts impairs CD94/NKG2A-dependent NK cytolysis after haplo-mismatched hematopoietic SCT

S Nguyen, V Beziat, N Dhedin, M Kuentz… - Bone marrow …, 2009 - nature.com
S Nguyen, V Beziat, N Dhedin, M Kuentz, JP Vernant, P Debre, V Vieillard
Bone marrow transplantation, 2009nature.com
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-γ 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 …
Abstract
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-γ 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-γ production. This implies that maturation of NK cells is the key to improved immune responses and transplantation outcome.
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