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单倍体不匹配造血干细胞移植后,干扰素-γ激活的急性髓系白血病母细胞上HLA-E上调会损害CD94/NKG2A依赖的自然杀伤细胞细胞溶解作用。

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

作者信息

Nguyen S, Beziat V, Dhedin N, Kuentz M, Vernant J P, Debre P, Vieillard V

机构信息

Laboratoire d'Immunologie Cellulaire et Tissulaire, Institut National de la Santé et de la Recherche Médicale U543, Hôpital Pitié-Salpêtrière, Paris, France.

出版信息

Bone Marrow Transplant. 2009 May;43(9):693-9. doi: 10.1038/bmt.2008.380. Epub 2008 Nov 17.

DOI:10.1038/bmt.2008.380
PMID:19011664
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-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.

摘要

急性髓系白血病(AML)患者单倍体相合造血干细胞移植(SCT)后产生的自然杀伤(NK)细胞具有特定的表型特征和功能受损,这可能会影响移植结果。我们发现,未成熟的CD56(明亮型)NK细胞产生的γ干扰素会上调AML原始细胞上HLA-E的细胞表面表达,并且这种上调通过CD94/NKG2A的介导保护白血病细胞免受NK介导的细胞裂解,CD94/NKG2A是单倍体相合SCT后NK细胞上过表达的一种抑制性受体。然而,移植两年后,成熟的NK细胞功能活跃,高细胞毒性和低γ干扰素产生证明了这一点。这意味着NK细胞的成熟是改善免疫反应和移植结果的关键。

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