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An Unusual CD56^brightCD16^low NK Cell Subset Dominates the Early Posttransplant Period following HLA-Matched Hematopoietic Stem Cell Transplantation¹

Nicolas Dulphy^2,3,*,,, Philippe Haas^2,*, Marc Busson^*, Stéphanie Belhadj, Régis Peffault de Latour^¶, Marie Robin^¶, Maryvonnick Carmagnat^*,, Pascale Loiseau^*,, Ryad Tamouza^*,, Catherine Scieux^||, Claire Rabian^*,,, James P. Di Santo^#,**, Dominique Charron^*,,, Anne Janin^,, Gérard Socié^,¶ and Antoine Toubert^*,,

^* Institut National de la Santé et de la Recherche Médicale, U662, Paris, France; Université Paris 7, Institut Universitaire d’Hématologie, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre d’Investigations Biomédicales "Hématologie Oncologie Greffe", Paris, France; Institut National de la Santé et de la Recherche Médicale U728, Paris, France; ^¶ Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Service d’Hématologie-Greffe de Moelle, Paris, France; ^|| Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Service de Virologie, Paris, France; ^# Cytokine and Lymphoid Development Unit, Institut Pasteur, Paris, France; and ^** Institut National de la Santé et de la Recherche Médicale U668, Paris, France

The expansion of the cytokine-producing CD56^bright NK cell subset is a main feature of lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated phenotypes and functions of CD56^bright and CD56^dim NK subsets from 43 HLA-matched non-T cell-depleted HSCT donor-recipient pairs. The early expansion of CD56^bright NK cells gradually declined in the posttransplant period but still persisted for at least 1 year and was characterized by the emergence of an unusual CD56^brightCD16^low subset with an intermediate maturation profile. The activating receptors NKG2D and NKp46, but also the inhibitory receptor NKG2A, were overexpressed compared with donor CD56^bright populations. Recipient CD56^bright NK cells produced higher amounts of IFN- than did their respective donors and were competent for degranulation. Intracellular perforin content was increased in CD56^bright NK cells as well as in T cells compared with donors. IL-15, the levels of which were increased in the posttranplant period, is a major candidate to mediate these changes. IL-15 serum levels and intracellular T cell perforin were significantly higher in recipients with acute graft-vs-host disease. Altogether, CD56^bright NK cells postallogeneic HSCT exhibit peculiar phenotypic and functional properties. Functional interactions between this subset and T cells may be important in shaping the immune response after HSCT.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by research grants from the Association de Recherche contre le Cancer (N.D.), Fondation pour la Recherche Médicale (fellowship DEA20040902110 to P.H.), Association Laurette Fugain, Cancéropôle Ile-de-France, and EC program FP6 ALLOSTEM (no. 503319).

² N.D. and P.H. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Nicolas Dulphy, Unité Institut National de la Santé et de la Recherche Médicale U662, Centre Hayem, Institut Universitaire d’Hématologie, Hôpital Saint-Louis, 1, avenue Claude Vellefaux, F-75010, Paris, France. E-mail address: nicolas.dulphy{at}univ-paris-diderot.fr

⁴ Abbreviations used in this paper: HSCT, hematopoietic stem cell transplantation; ADCC, antibody-dependent cellular cytotoxicity; aGVHD, acute GVHD; GVHD, graft-vs-host disease; GVL, graft vs leukemia; KIR, killer immunoglobulin-like receptor; MICA/B, MHC class I-related molecules A and B; NCR, natural cytotoxicity receptor; ULBP, UL16-binding protein.

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