HLA-E upregulation on IFN-γ-activated AML blasts impairs CD94/NKG2A-dependent NK cytolysis after haplo-mismatched hematopoietic SCT
HLA-E upregulation on IFN-γ-activated AML blasts impairs CD94/NKG2A-dependent NK cytolysis after haplo-mismatched hematopoietic SCT
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DOI：
10.1038/bmt.2008.380
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发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Vieillard, V.
中科院分区：
文献类型：
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作者：
Nguyen, S.;Beziat, V.;Vieillard, V.
在AML患者中，单倍体相合造血SCT后产生的自然杀伤（NK）细胞的特征在于可能影响移植结果的特定表型特征和功能受损。我们发现，IFN-γ产生的未成熟的CD 56（明亮）NK细胞上调细胞表面表达的HLA-E AML原始细胞，这种上调保护白血病细胞从NK介导的细胞溶解通过调解的CD 94/NKG 2A，抑制性受体过表达的半相合SCT后的NK细胞。然而，移植两年后，成熟的NK细胞功能活跃，表现为高细胞毒性和IFN-γ产生不足。这意味着NK细胞的成熟是改善免疫应答和移植结果的关键。骨髓移植（2009）43，693-699; doi：10.1038/bmt.2008.380; 2008年11月17日在线发表
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. Bone Marrow Transplantation (2009) 43, 693-699; doi:10.1038/bmt.2008.380; published online 17 November 2008