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Allografting

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

Bone Marrow Transplantation volume 43, pages 693–699 (2009)Cite this article

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 CD56bright 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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Acknowledgements

We gratefully acknowledge grant support received from the French Health Ministry (PHRC 1995) and from the association Cent pour Sang la Vie.

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Author notes

  1. S Nguyen and V Beziat: These authors contributed equally to this study.

Authors and Affiliations

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

    S Nguyen, V Beziat, P Debre & V Vieillard

  2. UPMC, Université Paris-6, Paris, France

    S Nguyen, V Beziat, P Debre & V Vieillard

  3. Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, Paris, France

    S Nguyen, N Dhedin & J P Vernant

  4. Service d'Hématologie Clinique, Hôpital Henri Mondor, Créteil, France

    M Kuentz

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Correspondence to V Vieillard.

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Nguyen, S., Beziat, V., Dhedin, N. et al. HLA-E upregulation on IFN-γ-activated AML blasts impairs CD94/NKG2A-dependent NK cytolysis after haplo-mismatched hematopoietic SCT. Bone Marrow Transplant 43, 693–699 (2009). https://doi.org/10.1038/bmt.2008.380

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